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Zolfaghari Emameh, R. Phytochemicals Modulate lncRNAs and Carbonic Anhydrases in Cancer. Encyclopedia. Available online: (accessed on 19 June 2024).
Zolfaghari Emameh R. Phytochemicals Modulate lncRNAs and Carbonic Anhydrases in Cancer. Encyclopedia. Available at: Accessed June 19, 2024.
Zolfaghari Emameh, Reza. "Phytochemicals Modulate lncRNAs and Carbonic Anhydrases in Cancer" Encyclopedia, (accessed June 19, 2024).
Zolfaghari Emameh, R. (2021, November 30). Phytochemicals Modulate lncRNAs and Carbonic Anhydrases in Cancer. In Encyclopedia.
Zolfaghari Emameh, Reza. "Phytochemicals Modulate lncRNAs and Carbonic Anhydrases in Cancer." Encyclopedia. Web. 30 November, 2021.
Phytochemicals Modulate lncRNAs and Carbonic Anhydrases in Cancer

Long non-coding RNAs (lncRNAs) are classified as a group of transcripts that regulate various biological processes, such as RNA processing, epigenetic control, and signaling pathways. According to recent studies, lncRNAs are dysregulated in cancer and play an important role in cancer incidence and spreading. There is also an association between lncRNAs and the overexpression of some tumor-associated proteins, including carbonic anhydrases II, IX, and XII (CA II, CA IX, and CA XII). Therefore, not only CA inhibition but also lncRNA modulation, could represent an attractive strategy for cancer prevention and therapy. Experimental studies have suggested that herbal compounds regulate the expression of many lncRNAs involved in cancer, such as HOTAIR (HOX transcript antisense RNA), H19, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), PCGEM1 (Prostate cancer gene expression marker 1), PVT1, etc. These plant-derived drugs or phytochemicals include resveratrol, curcumin, genistein, quercetin, epigallocatechin-3-galate, camptothecin, and 3,3'-diindolylmethane. More comprehensive information about lncRNA modulation via phytochemicals would be helpful for the administration of new herbal derivatives in cancer therapy.

phytochemicals long non-coding RNA carbonic anhydrase cancer modulator

1. Introduction

Phytochemicals are non-nutritive chemical components taken from various vegetables, fruits, beverages, and other green plants. Generally, the mechanism of action of these compounds occurs through the simulation of hormones, while they are known by their anti-oxidant and anti-inflammatory activities in cells [1][2][3][4]. To date, many phytochemicals have been identified and several are considered potential drugs due to their anticancer properties. They can be used as single chemopreventive drugs or synergistically with other routine anticancer drugs. This kind of anticancer drug administration can improve the efficacy of the treatment strategy, and optimally, with minimal or no side effects [5][6]. It has been suggested that phytochemicals act through the modulation of different signaling pathways via the regulation of significant molecular targets [7][8]

2. Biogenesis of lncRNA

After the discovery of coding and non-coding parts of the genome, it was suggested that non-coding sections may play an important role in cellular activities [9]. Furthermore, recent findings have suggested that lncRNAs function in various cancers, where their contribution is based on developmental and tissue specific expression patterns [10][11][12][13][14][15][16][17][18]. Both coding and non-coding genes carry genetic information with different functions. According to their location in the genome, lncRNAs can be divided into four groups: (1) the intergenic lncRNAs, which are located between two genes; (2) the sense or antisense lncRNAs, which may overlap with an exon of another transcript in the same or opposite direction; (3) the intronic lncRNAs, which reside within an intron and do not overlap with any exon; and (4) the processed transcripts, which reside in a locus where none of the transcript has an ORF and thus, do not fit into any other categories because of structural complexity (Figure 1).
Figure 1. The flow of genetic information encoding for mRNA and long non-coding RNA (lncRNA).
Three major properties of this RNA molecule were identified: (1) it might have or does not have an ORF for coding more than 100 amino acids; (2) there is no need for this section to produce a protein, but is still functional [19] and ; (3) it can contain both coding and non-coding domains [20][21][22].

3. Modulation of lncRNA by phytochemicals

lncRNAs are considered great targets for anticancer studies due to their potential tumor suppressor abilities. Several studies have suggested that the modulation of lncRNAs with various phytochemicals could be a novel option in cancer therapy. It has been clearly indicated that these lncRNAs are regulated by defined phytochemicals (Figure 2).
Figure 2. Regulation of long non-coding RNAs (lncRNAs) by natural compounds and their inhibition effects on cell (A) apoptosis, (B) proliferation, (C) migration, and (D) invasion. The inhibition relationships are denoted as red stop symbols, whereas positive interactions are denoted as normal blue arrows. CUR: Curcumin, GEN: Genistein, RSV: Resveratrol, ECGC: Epigallocatechin-3-gallate, CPT: Camptothecin, DIM: 3,3-diindolylmethane, QUE: Quercetin. The blue arrows show the modulation roles of phytochemicals, the red arrows show the induction role of phytochemicals, and the T bars show the inhibition role of phytochemicals on the lncRNAs.

4. Camptothecin (CPT)

Camptothecin (CPT, C20H16N2O4) is an alkaloid derived from a Chinese tree Camptotheca acuminate (happy tree). CPT has an inhibitory role in topoisomerase I and possesses antitumor activity [23][24][25]. CPT was demonstrated to suppress hypoxia-inducible factor 1 alpha (HIF-1α) -antisense RNA 1 in different human cancer types [26][27][23]. CPT also induces apoptosis in cardiovascular and kidney carcinomas, which results in an enhancement of the expression of antisense lncRNA. In another study, CPT treatment was shown to regulate the expression of lncRNA HIF-1α synergically with miR-17-5-p and miR-155 [28]. CPT has the ability to reduce CA IX expression in the cancer zone through the inhibition of angiogenesis and hypoxia. CPT has been conjugated to a linear, cyclodextrin-polyethylene glycol (CD-PEG) copolymer to form CRLX101 as a nanoparticle-drug conjugate (NDC). The conjugation step revealed that CRLX101 was more efficient than CPT in terms of the induction of apoptosis and supression of angiogenesis [29][30][31][32] (Table 1).
Table 1. Long non-coding RNAs (lncRNAs) and carbonic anhydrases (CAs) affected by phytochemicals.
Phytochemicals lncRNAs Carbonic Anhydrases (CAs) Ref
Camptothecin (CPT) HIF-1α CA IX [29][30][31][32]
Curcumin GAS5, HOTAIR, H19, AF086415, AK095147, RP1-179N16.3, MUDENG, AK056098, AK294004 CA II, CA IX, CA XII [33][34][35][36][37][38]
3,3′-diindolylmethane (DIM) PCGEM1, FOXM1 CA I, II, IV, VII [39]
Epigallocatechin-3-galate (ECGC) AT102202 CA II, IX [40][41]
Genistein HOTAIR CA II [42][43][44]
Quercetin DBH-AS1 CA I, II, III, IV, XII, XIV [45][46][47][48]
Resveratrol PCGEM1, PRNCR1, PCAT29, AK001796, MALAT1, u-Eleanor, LINC00978 CA I‒XV [34][49]

5. Curcumin

Curcumin (diferul[84]oylmethane) (C21H20O6 or C21H20O6) is a polyphenol derived from a perennial herbaceous plant, Curcuma longa [50]. This spicy yellow powder is used as an anti-inflammatory, antimicrobial, and antioxidant in traditional Asian medicine [51][52]. Curcumin acts as a chemopreventive and chemotherapeutic drug against various types of tumors, and is an important lncRNA regulator in cancers [53]. Petric et al. have shown that curcumin has an inhibitory effect on some oncogenic signaling pathways, including NF-kB, and induces apoptotic processes in breast cancer [2]. In another study, curcumin inhibited the overexpression of GAS5 in lung cancer by affecting signaling pathways, such as NF-kB, STAT3, and PI3K/Akt, to suppress tumor cell proliferation [54]. Curcumin also caused the modulation of tumor suppressor HOTAIR in pancreatic cancer [55], prostate cancer [56], hepatocellular carcinoma (HCC) [57][58], nasopharyngeal carcinoma (NPC) [59], breast cancer [60], lung cancer [61], and renal cancer [62][57][63][58][60][64][65]. It seems that the upregulation of HOTAIR has a controversial effect in terms of the occurrence of different cancer types and response to therapy methods, so radioresistance in breast cancer is enhanced by upregulated HOTAIR [60]. In addition, the expression level of HOTAIR is higher in renal cell carcinoma in comparison with normal kidney cells and a correlation has been shown between the upregulation of HOTAIR and distant metastasis in renal cell carcinoma malignancy [66]. Therefore, curcumin acts as a HOTAIR modulator, which consequently modulates the miR-19/PTEN/AKT/p53 axis in cancers [67].

6. 3,3′-diindolylmethane (DIM)

3,3′-Diindolylmethane (DIM, C17H14N2) is a known phytochemical compound derived from indole-3-carbinol (I3C) [68]. It is found in cruciferous vegetables like broccoli, cabbage, and kale [69]. DIM has an impact on signaling pathways and can regulate cell division, apoptosis, and angiogenesis in cancer cells [70]. It has been demonstrated that DIM inhibits PCGEM1 expression and induces apoptosis in prostate cancer [71]. Moreover, it has been observed that DIM indirectly suppresses the Akt/FOXM1 signaling cascade by regulating FOXM1 gene expression [72]. FOXM1 regulates various lncRNAs in some carcinomas [73]. Bioresponse formulated 3,3′-diindolylmethane (BR-DIM) decreases androgen receptor (AR) variants and AR3 expression in prostate cancer [71]. A study revealed that the combination of indolin-based compounds with sulfonamides can inhibit CA I, II, IV, and VII [39] (Table 1).

7. Epigallocatechin-3-galate (EGCG)

Epigallocatechin (EGCG, C15H14O7) is a known polyphenol flavonoid derived from almond and green tea [74][75][76][77][78][79]. This compound regulates the expression of non-coding RNAs in tumors and has notable anticancer, anti-inflammatory, and antioxidant features [2]. EGCG modulates various signaling pathways, such as NF-kB, MAPK, Akt, PI3K, PTEN, and mTORC1, as well as the expression of the estrogen receptor (ER) [80][81][82]. It has been shown that EGCG suppresses a lncRNA, AT102202, which downregulates the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) in human hepatocytes, leading to the uptake of cholesterol by the liver [83]. A study showed that polyphenol Epigallocatechin upregulates CA IX in breast cancer cells, which may possess strong antioxidative and antiapoptotic properties [40]. It has also been demonstrated that EGCG as a content of flavonoids in green tea has a suppression effect on CA II [41] (Table 1).

8. Genistein

Genistein (C15H10O5), a dietary soy isoflavone, is another phytochemical compound with in vitro and in vivo antitumor effects [84]. It has shown some anti-proliferation effects on many types of human cancers, such as breast, renal, and prostate cancers [2][85][86][87][88][89]. Genistein modulates the expression level of HOTAIR in breast cancer, which consequently modulates the activity of the PI3K/Akt signaling pathway [90]. Genistein suppresses the progression of renal cancer by inhibiting HOTAIR [85]. It was found that the miR-141 expression was upregulated, while the HOTAIR expression was downregulated, by genistein in cancer cells [84]. In prostate cancer, genistein reduced the HOTAIR and miR-34a expression synergically. Another study also suggested that genistein has antitumor effects in colorectal cancer by affecting HOTAIR [91]. In addition, genistein induces apoptosis in cancer cells, including breast, prostate, gastric, lung, pancreatic, melanoma, and renal cancers, by inhibiting several signaling pathways, such as Wnt and Akt [86][92]. The decreased expression of HOTAIR leads to apoptosis, which has been induced by genistein in multiple types of cancer [56]. In this case, most studies considered the correlation between phyto-isoflavones and -oestrogens in cervix, ovariectomy, uterus, and liver cancers through the modulatory effect of genistein on CA II expression [42][43][44] (Table 1).

9. Quercetin

Quercetin (C15H10O7) is a polyphenolic flavonoid with chemopreventive properties. This dietary antioxidant is derived from several plants and fruits, such as red grapes, broccoli, and some berries. Quercetin downregulated the expression of DBH-AS1 in hepatocellular carcinoma through its antiproliferative and antioxidant activities [93][94][95]. It was reported that quercetin acts as an inhibitor in different signaling pathways like Akt/mTOR/P70S6K and PI3K/AkT [96][97][98]. Most studies have confirmed the inhibition activity of quercetin on CA isoforms, including CA I, II, III, IV, XII, and XIV [45][46][47]. Recently, quercetin-modified metal–organic frameworks (Zr-MOF-QU) as the novel type of Zr-MOF nanoparticles have shown excellent efficiency for CA IX inhibition in tumor cells [48] (Table 1). Zr-MOF-QU seems to be used successfully in radiotherapy.

10. Resveratrol

Resveratrol (3,4′,5 tri-hydroxystilbene) (C14H12O3) is a natural polyphenol compound found in various plants and herbs, including blueberries, raspberries, mulberries, and the skin of grapes [99]. Resveratrol has anti-inflammatory and antiproliferative properties, as well as antitumor effects on various human cancers [100][101], including prostate [102][103], thyroid [104], colorectal [105][106], breast [107][108], lung [109][110], and bladder cancers [100][111][112][102][113]. Resveratrol inhibits the AR signaling pathway in prostate cancer by affecting PCGEM1 and PRNCR1 [114][115][116][117]. Another prostate cancer study revealed that resveratrol is a reverse potent stimulator in the reduction of PCAT29 expression induced by a cancer cell line [103]. Synergistic growth inhibition activity of resveratrol and AK001796 has been demonstrated in lung cancer [118]. There is also evidence that the treatment of lung cancer with resveratrol results in the downregulation of AK001796 expression. Studies have revealed that polyphenol resveratrol could inhibit CA I‒XV in cancers, so CA II was inhibited more efficiently [34][49] (Table 1).

11. The Mechanisms of lncRNA Regulation by Phytochemicals

In recent years, several lncRNAs with interfering properties have been identified in different types of cancers. Thus far, the exact mechanism of lncRNA regulation in normal physiology or cancer cells is still unknown [119][120]. There is some evidence suggesting that lncRNAs are involved in the regulation of gene expression via transcriptional and post-transcriptional mechanisms and chromatin modification [121]. Furthermore, previous studies have defined that phytochemicals change the dysregulation of lncRNAs in various cancer types [122][123].

12. Transcriptional and Post-Transcriptional Regulation of lncRNAs

TOP2A is a necessary element for the transcriptional activity of RNA polymerase II, which leads to a reduction of LS Pol II-mediated H19 transcription. Kujundzic and coworkers demonstrated that curcumin downregulates TOP2A expression and consequently inhibits H19 expression in tumor cell lines [124]. In another study, it was shown that curcumin regulates H19 through affecting the PI3K/Akt signaling pathway [125][126][127]. It was also shown that 3,3′-diindolylmethane inhibited the expression of PCGEM1 by banning its interaction with a nuclear RNA-binding protein, p54/nrb [71]. EGCG suppresses the promoter of the Cu(I) transport gene 1 (CTR1) in cancer cells, while it induces it through NEAT1, which is associated with hsa-miR-98-5p [128][129][130][131]. Furthermore, HOTAIR upregulates c-Myc in breast and ovarian cancers, which in turn promotes cancer cell proliferation [132]. Genistein downregulates the expression of HOTAIR at the transcription level in several cancers. The AR activation is a significant element in castration-resistant prostate cancer (CRPC) and increasing the expression level of HOTAIR [133].

13. Chromatin Modification by lncRNAs

lncRNAs are vital regulators of the genome structure, are able to interact with chromatin-modifying enzymes, and control the chromatin structure and accessibility to genetic information through reprogramming mechanisms [134][135]. The DNA methylation of genes inhibits the regulation of histone-modifying enzymes, which contributes to prostate cancer progression [103]. Several lncRNAs, such as PTENP1, Linc00963, PCGIM1, PRNCR1, CBR-3AS1, CTP1AS, GAS5, ANRIL, ANRASSF1, and PCAT1, upregulate the proliferation of cancer cells [22][136][137][103][138][139][140][141][142][143][144][145][146]. Resveratrol blocked the reduction of PCAT29 expression of this lncRNA in hepatocellular carcinoma [147]. HOTAIR can act as a mediator of proliferation, migration, invasion, and apoptosis in breast, liver, and colon cancer metastasis through genetic regulation [62][58][148]. Generally, lncRNAs are impartible vital molecules that are involved in gene modification and reprogramming. Phytochemicals, with their regulatory effects on lncRNAs, can be helpful as natural drugs for various cancer therapies.


  1. Block, G.; Patterson, B.; Subar, A. Fruit, vegetables, and cancer prevention: A review of the epidemiological evidence. Nutr. Cancer 1992, 18, 1–29.
  2. Petric, R.C.; Braicu, C.; Raduly, L.; Zanoaga, O.; Dragos, N.; Monroig, P.; Dumitrascu, D.; Berindan-Neagoe, I. Phytochemicals modulate carcinogenic signaling pathways in breast and hormone-related cancers. Oncotargets Ther. 2015, 8, 2053.
  3. Reddy, L.; Odhav, B.; Bhoola, K. Natural products for cancer prevention: A global perspective. Pharmacol. Ther. 2003, 99, 1–13.
  4. Steinmetz, K.A.; Potter, J.D. Vegetables, fruit, and cancer prevention: A review. J. Am. Diet. Assoc. 1996, 96, 1027–1039.
  5. Siddique, Y.H.; Ara, G.; Beg, T.; Gupta, J.; Afzal, M. Assessment of cell viability, lipid peroxidation and quantification of DNA fragmentation after the treatment of anticancerous drug mitomycin C and curcumin in cultured human blood lymphocytes. Exp. Toxicol. Pathol. 2010, 62, 503–508.
  6. Tan, W.; Lu, J.; Huang, M.; Li, Y.; Chen, M.; Wu, G.; Gong, J.; Zhong, Z.; Xu, Z.; Dang, Y. Anti-cancer natural products isolated from chinese medicinal herbs. Chin. Med. 2011, 6, 27.
  7. Tyagi, N.; Ghosh, P.C. Folate receptor mediated targeted delivery of ricin entrapped into sterically stabilized liposomes to human epidermoid carcinoma (KB) cells: Effect of monensin intercalated into folate-tagged liposomes. Eur. J. Pharm. Sci. 2011, 43, 343–353.
  8. Tyagi, N.; Rathore, S.S.; Ghosh, P.C. Enhanced killing of human epidermoid carcinoma (KB) cells by treatment with ricin encapsulated into sterically stabilized liposomes in combination with monensin. Drug Deliv. 2011, 18, 394–404.
  9. Gibb, E.A.; Brown, C.J.; Lam, W.L. The functional role of long non-coding RNA in human carcinomas. Mol. Cancer 2011, 10, 38.
  10. Castle, J.C.; Armour, C.D.; Löwer, M.; Haynor, D.; Biery, M.; Bouzek, H.; Chen, R.; Jackson, S.; Johnson, J.M.; Rohl, C.A. Digital genome-wide ncRNA expression, including SnoRNAs, across 11 human tissues using polyA-neutral amplification. PLoS ONE 2010, 5, e11779.
  11. Guffanti, A.; Iacono, M.; Pelucchi, P.; Kim, N.; Soldà, G.; Croft, L.J.; Taft, R.J.; Rizzi, E.; Askarian-Amiri, M.; Bonnal, R.J. A transcriptional sketch of a primary human breast cancer by 454 deep sequencing. BMC Genom. 2009, 10, 163.
  12. Loewer, S.; Cabili, M.N.; Guttman, M.; Loh, Y.-H.; Thomas, K.; Park, I.H.; Garber, M.; Curran, M.; Onder, T.; Agarwal, S. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat. Genet. 2010, 42, 1113.
  13. Maruyama, R.; Shipitsin, M.; Choudhury, S.; Wu, Z.; Protopopov, A.; Yao, J.; Lo, P.-K.; Bessarabova, M.; Ishkin, A.; Nikolsky, Y. Altered antisense-to-sense transcript ratios in breast cancer. Proc. Natl. Acad. Sci. USA 2012, 109, 2820–2824.
  14. Mercer, T.R.; Dinger, M.E.; Sunkin, S.M.; Mehler, M.F.; Mattick, J.S. Specific expression of long noncoding RNAs in the mouse brain. Proc. Natl. Acad. Sci. USA 2008, 105, 716–721.
  15. Perez, D.S.; Hoage, T.R.; Pritchett, J.R.; Ducharme-Smith, A.L.; Halling, M.L.; Ganapathiraju, S.C.; Streng, P.S.; Smith, D.I. Long, abundantly expressed non-coding transcripts are altered in cancer. Hum. Mol. Genet. 2007, 17, 642–655.
  16. Rinn, J.L.; Kertesz, M.; Wang, J.K.; Squazzo, S.L.; Xu, X.; Brugmann, S.A.; Goodnough, L.H.; Helms, J.A.; Farnham, P.J.; Segal, E. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 2007, 129, 1311–1323.
  17. Silva, J.M.; Perez, D.S.; Pritchett, J.R.; Halling, M.L.; Tang, H.; Smith, D.I. Identification of long stress-induced non-coding transcripts that have altered expression in cancer. Genomics 2010, 95, 355–362.
  18. Taft, R.J.; Pang, K.C.; Mercer, T.R.; Dinger, M.; Mattick, J.S. Non-coding RNAs: Regulators of disease. J. Pathol. 2010, 220, 126–139.
  19. Washietl, S.; Findeiß, S.; Müller, S.A.; Kalkhof, S.; von Bergen, M.; Hofacker, I.L.; Stadler, P.F.; Goldman, N. RNAcode: Robust discrimination of coding and noncoding regions in comparative sequence data. RNA 2011, 17, 578–594.
  20. Candeias, M.M.; Malbert-Colas, L.; Powell, D.J.; Daskalogianni, C.; Maslon, M.M.; Naski, N.; Bourougaa, K.; Calvo, F.; Fåhraeus, R. P53 mRNA controls p53 activity by managing Mdm2 functions. Nat. Cell Biol. 2008, 10, 1098.
  21. Martick, M.; Horan, L.H.; Noller, H.F.; Scott, W.G. A discontinuous hammerhead ribozyme embedded in a mammalian messenger RNA. Nature 2008, 454, 899.
  22. Poliseno, L.; Salmena, L.; Zhang, J.; Carver, B.; Haveman, W.J.; Pandolfi, P.P. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 2010, 465, 1033.
  23. Lorenzen, J.M.; Thum, T. Long noncoding RNAs in kidney and cardiovascular diseases. Nat. Rev. Nephrol. 2016, 12, 360.
  24. Moerter, C. Phase II study of camptothecin (NSC-100880) in the treatment of advanced gastrointestinal cancer. Cancer Chemother. Rep. 1972, 56, 95–101.
  25. Zeng, C.-W.; Zhang, X.-J.; Lin, K.-Y.; Ye, H.; Feng, S.-Y.; Zhang, H.; Chen, Y.-Q. Camptothecin induces apoptosis in cancer cells via microRNA-125b-mediated mitochondrial pathways. Mol. Pharmacol. 2012, 81, 578–586.
  26. Bertozzi, D.; Iurlaro, R.; Sordet, O.; Marinello, J.; Zaffaroni, N.; Capranico, G. Characterization of novel antisense HIF-1alpha transcripts in human cancers. Cell Cycle 2011, 10, 3189–3197.
  27. Yu, G.; Yao, W.; Wang, J.; Ma, X.; Xiao, W.; Li, H.; Xia, D.; Yang, Y.; Deng, K.; Xiao, H. LncRNAs expression signatures of renal clear cell carcinoma revealed by microarray. PLoS ONE 2012, 7, e42377.
  28. Bertozzi, D.; Marinello, J.; Manzo, S.G.; Fornari, F.; Gramantieri, L.; Capranico, G. The natural inhibitor of DNA topoisomerase I, camptothecin, modulates HIF-1alpha activity by changing miR expression patterns in human cancer cells. Mol. Cancer Ther. 2014, 13, 239–248.
  29. Lin, C.J.; Lin, Y.L.; Luh, F.; Yen, Y.; Chen, R.M. Preclinical effects of CRLX101, an investigational camptothecin-containing nanoparticle drug conjugate, on treating glioblastoma multiforme via apoptosis and antiangiogenesis. Oncotarget 2016, 7, 42408–42421.
  30. Gaur, S.; Wang, Y.; Kretzner, L.; Chen, L.; Yen, T.; Wu, X.; Yuan, Y.C.; Davis, M.; Yen, Y. Pharmacodynamic and pharmacogenomic study of the nanoparticle conjugate of camptothecin CRLX101 for the treatment of cancer. Nanomedicine 2014, 10, 1477–1486.
  31. Eliasof, S.; Lazarus, D.; Peters, C.G.; Case, R.I.; Cole, R.O.; Hwang, J.; Schluep, T.; Chao, J.; Lin, J.; Yen, Y.; et al. Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle. Proc. Natl. Acad. Sci. USA 2013, 110, 15127–15132.
  32. Cheng, J.; Khin, K.T.; Jensen, G.S.; Liu, A.; Davis, M.E. Synthesis of linear, beta-cyclodextrin-based polymers and their camptothecin conjugates. Bioconjug. Chem. 2003, 14, 1007–1017.
  33. Ramya, P.V.S.; Angapelly, S.; Angeli, A.; Digwal, C.S.; Arifuddin, M.; Babu, B.N.; Supuran, C.T.; Kamal, A. Discovery of curcumin inspired sulfonamide derivatives as a new class of carbonic anhydrase isoforms I, II, IX, and XII inhibitors. J. Enzym. Inhib. Med. Chem. 2017, 32, 1274–1281.
  34. Senturk, M.; Gulcin, I.; Beydemir, S.; Kufrevioglu, O.I.; Supuran, C.T. In Vitro inhibition of human carbonic anhydrase I and II isozymes with natural phenolic compounds. Chem. Biol. Drug Des. 2011, 77, 494–499.
  35. Karioti, A.; Carta, F.; Supuran, C.T. Phenols and Polyphenols as Carbonic Anhydrase Inhibitors. Molecules 2016, 21, 1649.
  36. Ahmed, M.; Qadir, M.A.; Hameed, A.; Arshad, M.N.; Asiri, A.M.; Muddassar, M. Sulfonamides containing curcumin scaffold: Synthesis, characterization, carbonic anhydrase inhibition and molecular docking studies. Bioorg. Chem. 2018, 76, 218–227.
  37. Kim, S.W.; Cha, M.J.; Lee, S.K.; Song, B.W.; Jin, X.; Lee, J.M.; Park, J.H.; Lee, J.D. Curcumin Treatment in Combination with Glucose Restriction Inhibits Intracellular Alkalinization and Tumor Growth in Hepatoma Cells. Int. J. Mol. Sci. 2019, 20, 2375.
  38. Aygul, I.; Yaylaci Karahalil, F.; Supuran, C.T. Investigation of the inhibitory properties of some phenolic standards and bee products against human carbonic anhydrase I and II. J. Enzym. Inhib. Med. Chem. 2016, 31, 119–124.
  39. Eldehna, W.M.; Al-Ansary, G.H.; Bua, S.; Nocentini, A.; Gratteri, P.; Altoukhy, A.; Ghabbour, H.; Ahmed, H.Y.; Supuran, C.T. Novel indolin-2-one-based sulfonamides as carbonic anhydrase inhibitors: Synthesis, in vitro biological evaluation against carbonic anhydrases isoforms I, II, IV and VII and molecular docking studies. Eur. J. Med. Chem. 2017, 127, 521–530.
  40. Guo, S.; Yang, S.; Taylor, C.; Sonenshein, G.E. Green tea polyphenol epigallocatechin-3 gallate (EGCG) affects gene expression of breast cancer cells transformed by the carcinogen 7,12-dimethylbenzanthracene. J. Nutr. 2005, 135, 2978S–2986S.
  41. Ferreira, N.; Cardoso, I.; Domingues, M.R.; Vitorino, R.; Bastos, M.; Bai, G.; Saraiva, M.J.; Almeida, M.R. Binding of epigallocatechin-3-gallate to transthyretin modulates its amyloidogenicity. FEBS Lett. 2009, 583, 3569–3576.
  42. Caldarelli, A.; Diel, P.; Vollmer, G. Effect of phytoestrogens on gene expression of carbonic anhydrase II in rat uterus and liver. J. Steroid Biochem. Mol. Biol. 2005, 97, 251–256.
  43. Norrby, M.; Madej, A.; Ekstedt, E.; Holm, L. Effects of genistein on oestrogen and progesterone receptor, proliferative marker Ki-67 and carbonic anhydrase localisation in the uterus and cervix of gilts after insemination. Anim. Reprod. Sci. 2013, 138, 90–101.
  44. Zhang, Y.; Li, Q.; Wan, H.Y.; Helferich, W.G.; Wong, M.S. Genistein and a soy extract differentially affect three-dimensional bone parameters and bone-specific gene expression in ovariectomized mice. J. Nutr. 2009, 139, 2230–2236.
  45. Ekinci, D.; Karagoz, L.; Ekinci, D.; Senturk, M.; Supuran, C.T. Carbonic anhydrase inhibitors: In vitro inhibition of alpha isoforms (hCA I, hCA II, bCA III, hCA IV) by flavonoids. J. Enzym. Inhib. Med. Chem. 2013, 28, 283–288.
  46. Sarikaya, S.B.; Gulcin, I.; Supuran, C.T. Carbonic anhydrase inhibitors: Inhibition of human erythrocyte isozymes I and II with a series of phenolic acids. Chem. Biol. Drug Des. 2010, 75, 515–520.
  47. Innocenti, A.; Beyza Ozturk Sarikaya, S.; Gulcin, I.; Supuran, C.T. Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I–XIV with a series of natural product polyphenols and phenolic acids. Bioorg. Med. Chem. 2010, 18, 2159–2164.
  48. Ma, T.; Liu, Y.; Wu, Q.; Luo, L.; Cui, Y.; Wang, X.; Chen, X.; Tan, L.; Meng, X. Quercetin-Modified Metal-Organic Frameworks for Dual Sensitization of Radiotherapy in Tumor Tissues by Inhibiting the Carbonic Anhydrase IX. ACS Nano 2019, 13, 4209–4219.
  49. Innocenti, A.; Gulcin, I.; Scozzafava, A.; Supuran, C.T. Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg. Med. Chem. Lett. 2010, 20, 5050–5053.
  50. Bolton, E.E.; Wang, Y.; Thiessen, P.A.; Bryant, S.H. PubChem: Integrated platform of small molecules and biological activities. In Annual Reports in Computational Chemistry; Elsevier: Amsterdam, The Netherlands, 2008; Volume 4, pp. 217–241.
  51. Esatbeyoglu, T.; Huebbe, P.; Ernst, I.; Chin, D.; Wagner, A.E.; Rimbach, G. Curcumin—From molecule to biological function. Angew. Chem. Int. Ed. 2012, 51, 5308–5332.
  52. Grynkiewicz, G.; Ślifirski, P. Curcumin and curcuminoids in quest for medicinal status. Acta Biochim. Pol. 2012, 59, 201–212.
  53. Anand, P.; Kunnumakkara, A.B.; Newman, R.A.; Aggarwal, B.B. Bioavailability of curcumin: Problems and promises. Mol. Pharm. 2007, 4, 807–818.
  54. De Bacco, F.; Luraghi, P.; Medico, E.; Reato, G.; Girolami, F.; Perera, T.; Gabriele, P.; Comoglio, P.M.; Boccaccio, C. Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer. Jnci J. Natl. Cancer Inst. 2011, 103, 645–661.
  55. Jiang, Y.; Li, Z.; Zheng, S.; Chen, H.; Zhao, X.; Gao, W.; Bi, Z.; You, K.; Wang, Y.; Li, W.; et al. The long non-coding RNA HOTAIR affects the radiosensitivity of pancreatic ductal adenocarcinoma by regulating the expression of Wnt inhibitory factor 1. Tumour Biol. J. Int. Soc. Oncodev. Biol. Med. 2016, 37, 3957–3967.
  56. Heubach, J.; Monsior, J.; Deenen, R.; Niegisch, G.; Szarvas, T.; Niedworok, C.; Schulz, W.A.; Hoffmann, M.J. The long noncoding RNA HOTAIR has tissue and cell type-dependent effects on HOX gene expression and phenotype of urothelial cancer cells. Mol. Cancer 2015, 14, 108.
  57. Geng, Y.J.; Xie, S.L.; Li, Q.; Ma, J.; Wang, G.Y. Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J. Int. Med Res. 2011, 39, 2119–2128.
  58. Yang, Z.; Zhou, L.; Wu, L.M.; Lai, M.C.; Xie, H.Y.; Zhang, F.; Zheng, S.S. Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann. Surg. Oncol. 2011, 18, 1243–1250.
  59. Ma, D.D.; Yuan, L.L.; Lin, L.Q. LncRNA HOTAIR contributes to the tumorigenesis of nasopharyngeal carcinoma via up-regulating FASN. Eur. Rev. Med Pharmacol. Sci. 2017, 21, 5143–5152.
  60. Zhou, Y.; Wang, C.; Liu, X.; Wu, C.; Yin, H. Long non-coding RNA HOTAIR enhances radioresistance in MDA-MB231 breast cancer cells. Oncol. Lett. 2017, 13, 1143–1148.
  61. Chen, J.; Shen, Z.; Zheng, Y.; Wang, S.; Mao, W. Radiotherapy induced Lewis lung cancer cell apoptosis via inactivating beta-catenin mediated by upregulated HOTAIR. Int. J. Clin. Exp. Pathol. 2015, 8, 7878–7886.
  62. Gupta, R.A.; Shah, N.; Wang, K.C.; Kim, J.; Horlings, H.M.; Wong, D.J.; Tsai, M.-C.; Hung, T.; Argani, P.; Rinn, J.L. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 2010, 464, 1071.
  63. Ma, M.Z.; Li, C.X.; Zhang, Y.; Weng, M.Z.; Zhang, M.D.; Qin, Y.Y.; Gong, W.; Quan, Z.W. Long non-coding RNA HOTAIR, a c-Myc activated driver of malignancy, negatively regulates miRNA-130a in gallbladder cancer. Mol. Cancer 2014, 13, 156.
  64. Yoshida, K.; Toden, S.; Ravindranathan, P.; Han, H.; Goel, A. Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2 subunit EZH2, and the lncRNA PVT1 expression. Carcinogenesis 2017, 38, 1036–1046.
  65. Hung, C.-L.; Wang, L.-Y.; Yu, Y.-L.; Chen, H.-W.; Srivastava, S.; Petrovics, G.; Kung, H.-J. A long noncoding RNA connects c-Myc to tumor metabolism. Proc. Natl. Acad. Sci. USA 2014, 111, 18697–18702.
  66. Pan, Y.; Wu, Y.; Hu, J.; Shan, Y.; Ma, J.; Ma, H.; Qi, X.; Jia, L. Long noncoding RNA HOTAIR promotes renal cell carcinoma malignancy through alpha-2, 8-sialyltransferase 4 by sponging microRNA-124. Cell Prolif. 2018, 51, e12507.
  67. Li, X.; Xie, W.; Xie, C.; Huang, C.; Zhu, J.; Liang, Z.; Deng, F.; Zhu, M.; Zhu, W.; Wu, R.; et al. Curcumin modulates miR-19/PTEN/AKT/p53 axis to suppress bisphenol A-induced MCF-7 breast cancer cell proliferation. Phytother. Res. 2014, 28, 1553–1560.
  68. Rakel, D. Integrative Medicine E-Book; Elsevier Health Sciences: Amsterdam, The Netherlands, 2012.
  69. Minich, D.M.; Bland, J.S. A review of the clinical efficacy and safety of cruciferous vegetable phytochemicals. Nutr. Rev. 2007, 65, 259–267.
  70. Licznerska, B.; Baer-Dubowska, W. Indole-3-carbinol and its role in chronic diseases. In Anti-Inflammatory Nutraceuticals and Chronic Diseases; Springer: New York, NY, USA, 2016; pp. 131–154.
  71. Ho, T.T.; Huang, J.; Zhou, N.; Zhang, Z.; Koirala, P.; Zhou, X.; Wu, F.; Ding, X.; Mo, Y.Y. Regulation of PCGEM1 by p54/nrb in prostate cancer. Sci. Rep. 2016, 6, 34529.
  72. Jin, H.; Park, M.H.; Kim, S.M. 3,3′-Diindolylmethane potentiates paclitaxel-induced antitumor effects on gastric cancer cells through the Akt/FOXM1 signaling cascade. Oncol. Rep. 2015, 33, 2031–2036.
  73. Cai, H.; Chen, J.; He, B.; Li, Q.; Li, Y.; Gao, Y. A FOXM1 related long non-coding RNA contributes to gastric cancer cell migration. Mol. Cell. Biochem. 2015, 406, 31–41.
  74. Li, G.-X.; Chen, Y.-K.; Hou, Z.; Xiao, H.; Jin, H.; Lu, G.; Lee, M.-J.; Liu, B.; Guan, F.; Yang, Z. Pro-oxidative activities and dose–response relationship of (−)-epigallocatechin-3-gallate in the inhibition of lung cancer cell growth: A comparative study in vivo and in vitro. Carcinogenesis 2010, 31, 902–910.
  75. McLarty, J.; Bigelow, R.L.; Smith, M.; Elmajian, D.; Ankem, M.; Cardelli, J.A. Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. Cancer Prev. Res. 2009, 2, 673–682.
  76. Moiseeva, E.P.; Manson, M.M. Dietary chemopreventive phytochemicals: Too little or too much? Cancer Prev. Res. 2009, 2, 611–616.
  77. Shimizu, M.; Deguchi, A.; Lim, J.T.; Moriwaki, H.; Kopelovich, L.; Weinstein, I.B. (−)-Epigallocatechin gallate and polyphenon E inhibit growth and activation of the epidermal growth factor receptor and human epidermal growth factor receptor-2 signaling pathways in human colon cancer cells. Clin. Cancer Res. 2005, 11, 2735–2746.
  78. Yang, C.S.; Wang, X.; Lu, G.; Picinich, S.C. Cancer prevention by tea: Animal studies, molecular mechanisms and human relevance. Nat. Rev. Cancer 2009, 9, 429.
  79. Hajipour, H.; Hamishehkar, H.; Nazari Soltan Ahmad, S.; Barghi, S.; Maroufi, N.F.; Taheri, R.A. Improved anticancer effects of epigallocatechin gallate using RGD-containing nanostructured lipid carriers. Artif. CellsNanomed. Biotechnol. 2018, 1–10.
  80. Kondo, A.; Takeda, T.; Li, B.; Tsuiji, K.; Kitamura, M.; Wong, T.F.; Yaegashi, N. Epigallocatechin-3-gallate potentiates curcumin’s ability to suppress uterine leiomyosarcoma cell growth and induce apoptosis. Int. J. Clin. Oncol. 2013, 18, 380–388.
  81. Kumazaki, M.; Noguchi, S.; Yasui, Y.; Iwasaki, J.; Shinohara, H.; Yamada, N.; Akao, Y. Anti-cancer effects of naturally occurring compounds through modulation of signal transduction and miRNA expression in human colon cancer cells. J. Nutr. Biochem. 2013, 24, 1849–1858.
  82. Srivastava, S.K.; Arora, S.; Averett, C.; Singh, S.; Singh, A.P. Modulation of microRNAs by phytochemicals in cancer: Underlying mechanisms and translational significance. Biomed. Res. Int. 2015, 2015.
  83. Salviano-Silva, A.; Lobo-Alves, S.C.; Almeida, R.C.; Malheiros, D.; Petzl-Erler, M.L. Besides Pathology: Long Non-Coding RNA in Cell and Tissue Homeostasis. Noncoding RNA 2018, 4, 3.
  84. Chiyomaru, T.; Fukuhara, S.; Saini, S.; Majid, S.; Deng, G.; Shahryari, V.; Chang, I.; Tanaka, Y.; Enokida, H.; Nakagawa, M. Long non-coding RNA HOTAIR is targeted and regulated by miR-141 in human cancer cells. J. Biol. Chem. 2014, 289, 12550–12565.
  85. Imai-Sumida, M.; Majid, S.; Dasgupta, P.; Kulkarni, P.; Saini, S.; Bhagirath, D.; Kato, T.; Maekawa, S.; Hashimoto, Y.; Shiina, M. Genistein inhibits renal cancer progression through long non-coding RNA HOTAIR suppression. Cancer Res. 2017, 77, 3449.
  86. Chiyomaru, T.; Yamamura, S.; Fukuhara, S.; Yoshino, H.; Kinoshita, T.; Majid, S.; Saini, S.; Chang, I.; Tanaka, Y.; Enokida, H.; et al. Genistein inhibits prostate cancer cell growth by targeting miR-34a and oncogenic HOTAIR. PLoS ONE 2013, 8, e70372.
  87. Phuah, N.H.; Nagoor, N.H. Regulation of microRNAs by natural agents: New strategies in cancer therapies. Biomed. Res. Int. 2014, 2014.
  88. Yao, Y.; Li, J.; Wang, L. Large intervening non-coding RNA HOTAIR is an indicator of poor prognosis and a therapeutic target in human cancers. Int. J. Mol. Sci. 2014, 15, 18985–18999.
  89. Zhang, A.; Zhao, J.C.; Kim, J.; Fong, K.-w.; Yang, Y.A.; Chakravarti, D.; Mo, Y.-Y.; Yu, J. LncRNA HOTAIR enhances the androgen-receptor-mediated transcriptional program and drives castration-resistant prostate cancer. Cell Rep. 2015, 13, 209–221.
  90. Chen, J.; Lin, C.; Yong, W.; Ye, Y.; Huang, Z. Calycosin and genistein induce apoptosis by inactivation of HOTAIR/p-Akt signaling pathway in human breast cancer MCF-7 cells. Cell. Physiol. Biochem. 2015, 35, 722–728.
  91. Zhou Du, T.F.; Verhaak, R.G.; Su, Z.; Zhang, Y.; Brown, M.; Chen, Y.; Liu, X.S. Integrative genomic analyses reveal clinically relevant long non-coding RNA in human cancer. Nat. Struct. Mol. Biol. 2013, 20, 908.
  92. Banerjee, S.; Li, Y.; Wang, Z.; Sarkar, F.H. Multi-targeted therapy of cancer by genistein. Cancer Lett. 2008, 269, 226–242.
  93. Russo, M.; Spagnuolo, C.; Tedesco, I.; Bilotto, S.; Russo, G.L. The flavonoid quercetin in disease prevention and therapy: Facts and fancies. Biochem. Pharmacol. 2012, 83, 6–15.
  94. Sudan, S.; Rupasinghe, H.V. Quercetin-3-O-glucoside induces human DNA topoisomerase II inhibition, cell cycle arrest and apoptosis in hepatocellular carcinoma cells. Anticancer Res. 2014, 34, 1691–1699.
  95. Zhao, J.-l.; Zhao, J.; Jiao, H.-J. Synergistic growth-suppressive effects of quercetin and cisplatin on HepG2 human hepatocellular carcinoma cells. Appl. Biochem. Biotechnol. 2014, 172, 784–791.
  96. Pan, F.; Zhu, L.; Lv, H.; Pei, C. Quercetin promotes the apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis by upregulating lncRNA MALAT1. Int. J. Mol. Med. 2016, 38, 1507–1514.
  97. Gao, J.-L.; Chen, Y.-G. Natural compounds regulate glycolysis in hypoxic tumor microenvironment. Biomed. Res. Int. 2015, 2015.
  98. Pratheeshkumar, P.; Son, Y.-O.; Divya, S.P.; Wang, L.; Turcios, L.; Roy, R.V.; Hitron, J.A.; Kim, D.; Dai, J.; Asha, P. Quercetin inhibits Cr (VI)-induced malignant cell transformation by targeting miR-21-PDCD4 signaling pathway. Oncotarget 2017, 8, 52118.
  99. Shrikanta, A.; Kumar, A.; Govindaswamy, V. Resveratrol content and antioxidant properties of underutilized fruits. J. Food Sci. Technol. 2015, 52, 383–390.
  100. Deng, L.L.; Chi, Y.Y.; Liu, L.; Huang, N.S.; Wang, L.; Wu, J. LINC00978 predicts poor prognosis in breast cancer patients. Sci. Rep. 2016, 6, 37936.
  101. Sinha, D.; Sarkar, N.; Biswas, J.; Bishayee, A. Resveratrol for breast cancer prevention and therapy: Preclinical evidence and molecular mechanisms. Semin. Cancer Biol. 2016, 40–41, 209–232.
  102. Zook, P.A. Chemopreventive Effects of Pterostilbene in Metastatic Prostate Cancer Cells. Master’s Thesis, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA, 2014.
  103. Al Aameri, R.F.H.; Sheth, S.; Alanisi, E.M.A.; Borse, V.; Mukherjea, D.; Rybak, L.P.; Ramkumar, V. Tonic suppression of PCAT29 by the IL-6 signaling pathway in prostate cancer: Reversal by resveratrol. PLoS ONE 2017, 12, e0177198.
  104. Li, Y.T.; Tian, X.T.; Wu, M.L.; Zheng, X.; Kong, Q.Y.; Cheng, X.X.; Zhu, G.W.; Liu, J.; Li, H. Resveratrol Suppresses the Growth and Enhances Retinoic Acid Sensitivity of Anaplastic Thyroid Cancer Cells. Int. J. Mol. Sci. 2018, 19, 1030.
  105. Li, R.; Ma, X.; Song, Y.; Zhang, Y.; Xiong, W.; Li, L.; Zhou, L. Anti-colorectal cancer targets of resveratrol and biological molecular mechanism: Analyses of network pharmacology, human and experimental data. J. Cell. Biochem. 2019.
  106. Liu, Z.; Wu, X.; Lv, J.; Sun, H.; Zhou, F. Resveratrol induces p53 in colorectal cancer through SET7/9. Oncol. Lett. 2019, 17, 3783–3789.
  107. He, X.; Wang, Y.; Zhu, J.; Orloff, M.; Eng, C. Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling. Cancer Lett. 2011, 301, 168–176.
  108. Hu, C.; Liu, Y.; Teng, M.; Jiao, K.; Zhen, J.; Wu, M.; Li, Z. Resveratrol inhibits the proliferation of estrogen receptor-positive breast cancer cells by suppressing EZH2 through the modulation of ERK1/2 signaling. Cell Biol. Toxicol. 2019.
  109. Liu, D.; He, B.; Lin, L.; Malhotra, A.; Yuan, N. Potential of curcumin and resveratrol as biochemical and biophysical modulators during lung cancer in rats. Drug Chem. Toxicol. 2019, 42, 328–334.
  110. Monteillier, A.; Voisin, A.; Furrer, P.; Allemann, E.; Cuendet, M. Intranasal administration of resveratrol successfully prevents lung cancer in A/J mice. Sci. Rep. 2018, 8, 14257.
  111. Ji, Q.; Liu, X.; Fu, X.; Zhang, L.; Sui, H.; Zhou, L.; Sun, J.; Cai, J.; Qin, J.; Ren, J. Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/β-catenin signal pathway. PLoS ONE 2013, 8, e78700.
  112. Tomita, S.; Abdalla, M.O.A.; Fujiwara, S.; Matsumori, H.; Maehara, K.; Ohkawa, Y.; Iwase, H.; Saitoh, N.; Nakao, M. A cluster of noncoding RNAs activates the ESR1 locus during breast cancer adaptation. Nat. Commun. 2015, 6, 6966.
  113. Zhang, D.; Yang, X.; Li, H.; Chong, T. MP39-13 resveratrol sensitizes bladder cancer cells to trail-induced apoptosis. J. Urol. 2014, 191, e430–e431.
  114. Gao, S.; Liu, G.Z.; Wang, Z. Modulation of androgen receptor-dependent transcription by resveratrol and genistein in prostate cancer cells. Prostate 2004, 59, 214–225.
  115. Harada, N.; Murata, Y.; Yamaji, R.; Miura, T.; Inui, H.; Nakano, Y. Resveratrol down-regulates the androgen receptor at the post-translational level in prostate cancer cells. J. Nutr. Sci. Vitaminol. 2007, 53, 556–560.
  116. Mitchell, S.H.; Zhu, W.; Young, C.Y. Resveratrol inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Cancer Res. 1999, 59, 5892–5895.
  117. Shi, W.-F.; Leong, M.; Cho, E.; Farrell, J.; Chen, H.-C.; Tian, J.; Zhang, D. Repressive effects of resveratrol on androgen receptor transcriptional activity. PLoS ONE 2009, 4, e7398.
  118. Yang, Q.; Xu, E.; Dai, J.; Liu, B.; Han, Z.; Wu, J.; Zhang, S.; Peng, B.; Zhang, Y.; Jiang, Y. A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol. Appl. Pharmacol. 2015, 285, 79–88.
  119. Cheetham, S.; Gruhl, F.; Mattick, J.; Dinger, M. Long noncoding RNAs and the genetics of cancer. Br. J. Cancer 2013, 108, 2419.
  120. Prensner, J.R.; Chinnaiyan, A.M. The emergence of lncRNAs in cancer biology. Cancer Discov. 2011, 1, 391–407.
  121. Ponting, C.P.; Oliver, P.L.; Reik, W. Evolution and functions of long noncoding RNAs. Cell 2009, 136, 629–641.
  122. Budisan, L.; Gulei, D.; Zanoaga, O.M.; Irimie, A.I.; Sergiu, C.; Braicu, C.; Gherman, C.D.; Berindan-Neagoe, I. Dietary Intervention by Phytochemicals and Their Role in Modulating Coding and Non-Coding Genes in Cancer. Int. J. Mol. Sci. 2017, 18, 1178.
  123. Debnath, T.; Deb Nath, N.C.; Kim, E.K.; Lee, K.G. Role of phytochemicals in the modulation of miRNA expression in cancer. Food Funct. 2017, 8, 3432–3442.
  124. Novak Kujundžić, R.; Grbeša, I.; Ivkić, M.; Katdare, M.; Gall-Trošelj, K. Curcumin downregulates H19 gene transcription in tumor cells. J. Cell. Biochem. 2008, 104, 1781–1792.
  125. Celton-Morizur, S.; Merlen, G.; Couton, D.; Margall-Ducos, G.; Desdouets, C. The insulin/Akt pathway controls a specific cell division program that leads to generation of binucleated tetraploid liver cells in rodents. J. Clin. Investig. 2009, 119, 1880–1887.
  126. Shoshani, O.; Zipori, D.; Shani, N. The tissue specific nature of mesenchymal stem/stromal cells: Gaining better understanding for improved clinical outcomes. Rna Dis. 2015, 2.
  127. Wang, G.; Lunardi, A.; Zhang, J.; Chen, Z.; Ala, U.; Webster, K.A.; Tay, Y.; Gonzalez-Billalabeitia, E.; Egia, A.; Shaffer, D.R. Zbtb7a suppresses prostate cancer through repression of a Sox9-dependent pathway for cellular senescence bypass and tumor invasion. Nat. Genet. 2013, 45, 739.
  128. Jiang, P.; Wu, X.; Wang, X.; Huang, W.; Feng, Q. NEAT1 upregulates EGCG-induced CTR1 to enhance cisplatin sensitivity in lung cancer cells. Oncotarget 2016, 7, 43337.
  129. Kalayda, G.V.; Wagner, C.H.; Jaehde, U. Relevance of copper transporter 1 for cisplatin resistance in human ovarian carcinoma cells. J. Inorg. Biochem. 2012, 116, 1–10.
  130. Larson, C.A.; Blair, B.G.; Safaei, R.; Howell, S.B. The role of the mammalian copper transporter 1 in the cellular accumulation of platinum-based drugs. Mol. Pharmacol. 2009, 75, 324–330.
  131. Tsai, C.-Y.; Larson, C.A.; Safaei, R.; Howell, S.B. Molecular modulation of the copper and cisplatin transport function of CTR1 and its interaction with IRS-4. Biochem. Pharmacol. 2014, 90, 379–387.
  132. Bhan, A.; Soleimani, M.; Mandal, S.S. Long noncoding RNA and cancer: A new paradigm. Cancer Res. 2017, 77, 3965–3981.
  133. Yoon, J.-H.; Abdelmohsen, K.; Kim, J.; Yang, X.; Martindale, J.L.; Tominaga-Yamanaka, K.; White, E.J.; Orjalo, A.V.; Rinn, J.L.; Kreft, S.G. Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination. Nat. Commun. 2013, 4, 2939.
  134. Han, P.; Chang, C.-P. Long non-coding RNA and chromatin remodeling. Rna Biol. 2015, 12, 1094–1098.
  135. Onder, T.T.; Kara, N.; Cherry, A.; Sinha, A.U.; Zhu, N.; Bernt, K.M.; Cahan, P.; Marcarci, B.O.; Unternaehrer, J.; Gupta, P.B.; et al. Chromatin-modifying enzymes as modulators of reprogramming. Nature 2012, 483, 598–602.
  136. Mourtada-Maarabouni, M.; Pickard, M.R.; Hedge, V.L.; Farzaneh, F.; Williams, G.T. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene 2009, 28, 195–208.
  137. Srikantan, V.; Zou, Z.; Petrovics, G.; Xu, L.; Augustus, M.; Davis, L.; Livezey, J.R.; Connell, T.; Sesterhenn, I.A.; Yoshino, K.; et al. PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer. Proc. Natl. Acad. Sci. USA 2000, 97, 12216–12221.
  138. Beckedorff, F.C.; Ayupe, A.C.; Crocci-Souza, R.; Amaral, M.S.; Nakaya, H.I.; Soltys, D.T.; Menck, C.F.; Reis, E.M.; Verjovski-Almeida, S. The intronic long noncoding RNA ANRASSF1 recruits PRC2 to the RASSF1A promoter, reducing the expression of RASSF1A and increasing cell proliferation. PLoS Genet. 2013, 9, e1003705.
  139. Chung, S.; Nakagawa, H.; Uemura, M.; Piao, L.; Ashikawa, K.; Hosono, N.; Takata, R.; Akamatsu, S.; Kawaguchi, T.; Morizono, T. Association of a novel long non-coding RNA in 8q24 with prostate cancer susceptibility. Cancer Sci. 2011, 102, 245–252.
  140. Cui, Z.; Ren, S.; Lu, J.; Wang, F.; Xu, W.; Sun, Y.; Wei, M.; Chen, J.; Gao, X.; Xu, C. The prostate cancer-up-regulated long noncoding RNA PlncRNA-1 modulates apoptosis and proliferation through reciprocal regulation of androgen receptor. Urol. Oncol. 2003, 31, 1117–1123.
  141. Malik, R.; Patel, L.; Prensner, J.R.; Shi, Y.; Iyer, M.K.; Subramaniyan, S.; Carley, A.; Niknafs, Y.S.; Sahu, A.; Han, S. The lncRNA PCAT29 inhibits oncogenic phenotypes in prostate cancer. Mol. Cancer Res. 2014, 12, 1081–1087.
  142. Poliseno, L.; Salmena, L.; Riccardi, L.; Fornari, A.; Song, M.S.; Hobbs, R.M.; Sportoletti, P.; Varmeh, S.; Egia, A.; Fedele, G. Identification of the miR-106b~25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation. Sci. Signal. 2010, 3, ra29.
  143. Prensner, J.R.; Iyer, M.K.; Balbin, O.A.; Dhanasekaran, S.M.; Cao, Q.; Brenner, J.C.; Laxman, B.; Asangani, I.A.; Grasso, C.S.; Kominsky, H.D. Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nat. Biotechnol. 2011, 29, 742.
  144. Takayama, K.i.; Horie-Inoue, K.; Katayama, S.; Suzuki, T.; Tsutsumi, S.; Ikeda, K.; Urano, T.; Fujimura, T.; Takagi, K.; Takahashi, S. Androgen-responsive long noncoding RNA CTBP1-AS promotes prostate cancer. EMBO J. 2013, 32, 1665–1680.
  145. Wang, L.; Han, S.; Jin, G.; Zhou, X.; Li, M.; Ying, X.; Wang, L.; Wu, H.; Zhu, Q. Linc00963: A novel, long non-coding RNA involved in the transition of prostate cancer from androgen-dependence to androgen-independence. Int. J. Oncol. 2014, 44, 2041–2049.
  146. Yap, K.L.; Li, S.; Muñoz-Cabello, A.M.; Raguz, S.; Zeng, L.; Mujtaba, S.; Gil, J.; Walsh, M.J.; Zhou, M.-M. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol. Cell 2010, 38, 662–674.
  147. Zamani, M.; Sadeghizadeh, M.; Behmanesh, M.; Najafi, F. Dendrosomal curcumin increases expression of the long non-coding RNA gene MEG3 via up-regulation of epi-miRs in hepatocellular cancer. Phytomedicine 2015, 22, 961–967.
  148. Zhang, J.; Zhang, P.; Wang, L.; Piao, H.-l.; Ma, L. Long non-coding RNA HOTAIR in carcinogenesis and metastasis. Acta Biochim. Biophys. Sin. 2013, 46, 1–5.
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