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Carvalho De Oliveira, J. Non-Coding RNAs in Tamoxifen Resistance. Encyclopedia. Available online: (accessed on 24 June 2024).
Carvalho De Oliveira J. Non-Coding RNAs in Tamoxifen Resistance. Encyclopedia. Available at: Accessed June 24, 2024.
Carvalho De Oliveira, Jaqueline. "Non-Coding RNAs in Tamoxifen Resistance" Encyclopedia, (accessed June 24, 2024).
Carvalho De Oliveira, J. (2021, August 06). Non-Coding RNAs in Tamoxifen Resistance. In Encyclopedia.
Carvalho De Oliveira, Jaqueline. "Non-Coding RNAs in Tamoxifen Resistance." Encyclopedia. Web. 06 August, 2021.
Non-Coding RNAs in Tamoxifen Resistance

Despite the clinical efficacy of Tam, intrinsic or acquired resistance is an important obstacle limiting the success of ER + breast cancer patient treatment. It is a challenge that needs to be overcome to improve the prognosis of these patients. The main mechanisms of resistance to tamoxifen can be divided according to different causes: mechanisms that involve genetic mutations and lead to loss or gain of function of the receptor and mechanisms that modulate other protumorigenic pathways, including other receptors involved in estrogen’s pathway of action.

breast cancer estrogen receptor tamoxifen endocrine resistance ncRNA lncRNA microRNA

1. Introduction

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality among women [1]. Breast tumors can be classified in clinical practice as hormone receptor and/or HER2 positive (HR+ and/or HER2+) vs negative (HR- and/or HER2-) by immunohistochemical detection or as luminal A, luminal B, HER2-enriched and basal-like according to transcriptome profiling using gene signatures such as PAM50 [2]. Hormone receptors include the estrogen receptor alpha (ERα), the main driver of breast cancer cell proliferation, and the progesterone receptor (PR), a gene regulated by ER, both acting as hormone-dependent transcription factors. HR+ tumors are positive for ER and/or progesterone receptor (PR). The HR+HER2- subtype is the most common, representing around 73% of all occurrences, and generally has a good prognosis. The HR+HER2+ subtype has a higher cell proliferation index and usually a more aggressive phenotype, constituting 11% of occurrences [3].

Breast cancer classification and the development of targeted therapies has considerably improved treatment options and patient prognosis [4]. The subtypes that are positive for the estrogen receptor usually respond to endocrine therapies targeting the estrogen receptor (ER) pathway, based on antiestrogens, which include selective ER modulators (SERMs) and selective ER downregulators (SERDs), or on aromatase inhibitors (AIs), which prevent endogenous production of estrogens [5]. One of the most commonly prescribed first-line SERM for hormone responsive subtypes is tamoxifen [6]. Tamoxifen (Tam) is a highly efficient SERM widely used for treatment of all stages of breast cancer in pre- and post-menopausal women. It binds ER and blocks its transcriptional activity. Tam use in the clinic has led to a drop in the recurrence rate by 50% at 5 years and 30% lower during the next 5 years [7]. However, approximately 50% of advanced ER-positive breast tumors are intrinsically resistant to tamoxifen and about 40% of patients receiving adjuvant tamoxifen eventually relapse [8].

The mechanisms that are involved in Tam resistance are complex and involve multiple signaling pathways [9][10]. Recently, roles for microRNAs and lncRNAs in controlling ER expression and/or tamoxifen action have been described, but the underlying mechanisms are still little explored. In this review, we will discuss the current state of knowledge on the roles of microRNAs and lncRNAs in the main mechanisms of tamoxifen resistance.

2. Estrogens and Estrogen Receptor Alpha

Estrogens are mitogenic hormones that play crucial roles in normal breast development, but also in carcinogenesis. They are predominantly synthesized in the ovaries of premenopausal women and to a lesser extent in peripheral tissues, including breast tissue. In postmenopausal women, estrogens are only produced in extragonadal peripheral tissues [11].

The estrogen receptor alpha (ERα) is one of the most significant biological markers for the diagnosis/prognosis of breast cancer and its accurate detection is important for therapeutic choice in BC patients. ERα is member of the nuclear receptor superfamily of ligand activated transcription factors [12][13]. There are two functionally distinct ERs: ERα and ERβ. The human ESR1 gene, which encodes ERα is located on chromosome 6 while the human ESR2 gene, coding for ERβ, is located on chromosome 14 [14][15]. These receptors have different and often opposite effects and the proliferative response caused by estrogens in breast epithelial cells is thought to be the result of a balance between ERα and ERβ signaling. While ERα has a proliferative effect on breast cells, acting as a transcriptional activator of genes associated with cell survival and proliferation, the role of ERβ is usually antiproliferative and proapoptotic [16][17]. However, ERα is overexpressed in ER+ tumors while ERβ expression is reduced.

The ERα is a 66 kDa nuclear protein and its transcriptional activity is ligand-dependent. Estrogens bind to the receptor and change its conformation, inducing binding to specific target DNA sequences called estrogen response elements (EREs) [12][13]. On DNA, the estrogen-ERα complex interacts with coregulatory proteins, modulating the transcription of genes involved in cell cycle regulation, DNA replication, cell differentiation, cell survival, and angiogenesis [14][18]. The estrogen-ER complex can also act on non-nuclear pathways through the regulation of membrane receptors (for example, IGFR, FGFR, and HER2) and kinases (for example, mitogen activated protein kinases, receptor tyrosine kinases, PI3K, AKT, mTOR, Src, and CDK4/6) [14][18].

The ESR1 gene also encodes ER variants, such as ERα36 and ERα46 [19][20]. ERα36 has a novel noncoding exon as its first exon and also a unique 27 amino acid domain that replaces the last 138 amino acids in ERα66, and as a result lacks both transcription activation domains (AF-1 and AF-2) [21]. ERα46 is a truncated form that lacks the transactivation function domain 1 (AF1) and functions to inhibit the AF1 activity of the full length ERα66 [22].

3. Mechanisms of Tamoxifen Resistance

ER isoforms, without gene mutations, may also be associated with Tam resistance. Although tamoxifen is an antagonist of ERα66, it activates ERα36. This activation might play critical roles in intrinsic and acquired Tam resistance [23]. Additionally, the ER-α46 variant enhances sensitivity to estrogens in breast cancer cells [22].

Some of the cellular mechanisms related to Tam resistance involve alternative oncogenic signaling pathways that can provide tumors with estrogen-independent stimuli for proliferation and survival ( Figure 1 ). An example is the activation of the ERBB2 pathway (Erb-B2 tyrosine receptor kinase 2 or HER2), known to reduce sensitivity to tamoxifen [24][25]. RBP2 (retinoblastoma-binding protein 2), also known as KDM5A (lysine demethylase 5A), physically interacts with ER, increases the stability of the EGFR and HER2 proteins, and promotes activation of the PI3K/AKT pathway, inducing tamoxifen resistance [26].

The phosphoinositide 3-kinase/Akt/mammalian target of the rapamycin (PI3K/Akt/mTOR) pathway is a cell signaling pathway that plays an important role in controlling cell cycle, survival, and cell growth [27]. The PI3K /AKT/mTOR pathway is dysregulated in many types of cancers. In breast cancer, it can lead to the resistance to endocrine therapy [28]. Indeed, inhibiting this pathway improved the effectiveness of tamoxifen in cultured cells [29].

Thus, defects in several signaling pathways can lead to resistance to Tam. The study of non-coding RNAs that interfere with either ER expression or with pathways involved in Tam resistance has added another layer of complexity to these mechanisms.

4. Non-Coding RNAs

Advances in sequencing technologies and computational approaches in the past few decades revealed that 75–85% of the genome is transcribed, although less than 3% of the human genome represents coding gene exons [30][31][32][33][34][35]. The remaining transcripts are non-coding RNAs (ncRNAs) and can be divided in subclasses. Ribosomal and transfer RNAs are the best known non-coding RNAs. However, in the past decade, increasing attention has been given to other classes of non-coding RNAs such as microRNAs, long non-coding RNAs, and circular RNAs, among others, notably for their roles in the regulation of gene expression and chromatin structure.

MicroRNAs (miRNAs/miRs) are small (approximately 18–25 nucleotide long) non-coding RNAs that, most of the time, interact with the 3′UTR of target mRNAs and post-transcriptionally regulate their expression by mRNA cleavage or by inhibition of translation [36]. Dysregulated miRNA expression is frequently associated with hallmarks in cancer development and resistance to therapies [37][38]. In breast cancer, several reports suggested that miRNAs might have an essential role in Tam resistance by the regulation of genes in previously described pathways [39][40][41][42][43].

Long non-coding RNAs (lncRNAs) are a class of non-coding transcripts that are over 200 nucleotide long [44][45]. LncRNAs have similarities with mRNAs in terms of length, transcription and splicing structure, yet lack protein-coding potential due to the absence of sizeable open reading frames, although some lncRNA may encode small functional peptides [44][46][47]. LncRNAs are located in intergenic, intronic or exonic loci, and can be imprinted. They may overlap with protein-coding genes in a sense or antisense direction [46][48][49][50][51].

There is growing evidence indicating that many lncRNAs are expressed in a temporal and tissue-specific manner and play a role in gene regulation through different mechanisms [45][49][50][51][52][53]. Accumulating evidence suggests that some lncRNAs may be key regulators of biological processes like imprinting [54][55], pluripotency [56][57][58][59] , cell differentiation [57][58], DNA damage response [51], cell apoptosis [53], inflammatory and immune responses [60]. Mutations, polymorphisms or altered expression patterns of lncRNAs have been associated with the progression and/or severity of several diseases, including breast cancer [51][61][62][63][64]. More recently, lncRNA deregulation has also been associated with Tam resistance in breast cancer cells [65].


  1. Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249.
  2. Eroles, P.; Bosch, A.; Pérez-Fidalgo, J.A.; Lluch, A. Molecular biology in breast cancer: Intrinsic subtypes and signaling pathways. Cancer Treat. Rev. 2012, 38, 698–707.
  3. American Cancer Society. Breast Cancer Facts & Figures 2019–2020; American Cancer Society: Atlanta, GA, USA, 2019.
  4. Harbeck, N.; Gnant, M. Breast cancer. Lancet 2017, 389, 1134–1150.
  5. Traboulsi, T.; El Ezzy, M.; Gleason, J.; Mader, S. Antiestrogens: Structure-activity relationships and use in breast cancer treatment. J. Mol. Endocrinol. 2017, 58, R15–R31.
  6. Abe, O.; Abe, R.; Enomoto, K.; Kikuchi, K.; Koyama, H.; Masuda, H.; Nomura, Y.; Sakai, K.; Sugimachi, K.; Tominaga, T.; et al. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet 2005, 365, 1687–1717.
  7. Pan, H.; Gray, R.; Braybrooke, J.; Davies, C.; Taylor, C.; McGale, P.; Peto, R.; Pritchard, K.I.; Bergh, J.; Dowsett, M.; et al. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. N. Engl. J. Med. 2017, 377, 1836–1846.
  8. Ring, A.; Dowsett, M. Mechanisms of tamoxifen resistance. Endocr. Relat. Cancer 2004, 11, 643–658.
  9. Kangaspeska, S.; Hultsch, S.; Jaiswal, A.; Edgren, H.; Mpindi, J.-P.; Eldfors, S.; Brück, O.; Aittokallio, T.; Kallioniemi, O. Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer. BMC Cancer 2016, 16, 378.
  10. Hultsch, S.; Kankainen, M.; Paavolainen, L.; Kovanen, R.-M.; Ikonen, E.; Kangaspeska, S.; Pietiäinen, V.; Kallioniemi, O. Association of tamoxifen resistance and lipid reprogramming in breast cancer. BMC Cancer 2018, 18, 1–14.
  11. Radhi, S. Molecular Changes During Breast Cancer and Mechanisms of Endocrine Therapy Resistance. Prog. Mol. Biol. Transl. Sci. 2016, 144, 539–562.
  12. Sanchez, R.; Nguyen, D.; Rocha, W.; White, J.H.; Mader, S. Diversity in the mechanisms of gene regulation by estrogen receptors. BioEssays 2002, 24, 244–254.
  13. Cotnoir-White, D.; Laperrière, D.; Mader, S. Evolution of the repertoire of nuclear receptor binding sites in genomes. Mol. Cell. Endocrinol. 2011, 334, 76–82.
  14. Brufsky, A.M.; Dickler, M.N. Estrogen Receptor-Positive Breast Cancer: Exploiting Signaling Pathways Implicated in Endocrine Resistance. Oncologist 2018, 23, 528–539.
  15. Begam, A.J.; Jubie, S.; Nanjan, M. Estrogen receptor agonists/antagonists in breast cancer therapy: A critical review. Bioorg. Chem. 2017, 71, 257–274.
  16. Stender, J.D.; Frasor, J.; Komm, B.; Chang, K.C.N.; Kraus, W.L.; Katzenellenbogen, B.S. Estrogen-Regulated Gene Networks in Human Breast Cancer Cells: Involvement of E2F1 in the Regulation of Cell Proliferation. Mol. Endocrinol. 2007, 21, 2112–2123.
  17. Bourdeau, V.; Deschênes, J.; Laperrière, D.; Aid, M.; White, J.; Mader, S. Mechanisms of primary and secondary estrogen target gene regulation in breast cancer cells. Nucleic Acids Res. 2007, 36, 76–93.
  18. Glück, S. Consequences of the Convergence of Multiple Alternate Pathways on the Estrogen Receptor in the Treatment of Metastatic Breast Cancer. Clin. Breast Cancer 2017, 17, 79–90.
  19. Wang, Z.-Y.; Yin, L. Estrogen receptor alpha-36 (ER-α36): A new player in human breast cancer. Mol. Cell. Endocrinol. 2015, 418, 193–206.
  20. Penot, G.; Le Péron, C.; Mérot, Y.; Grimaud-Fanouillère, E.; Ferriere, F.; Boujrad, N.; Kah, O.; Saligaut, C.; Ducouret, B.; Métivier, R.; et al. The Human Estrogen Receptor-α Isoform hERα46 Antagonizes the Proliferative Influence of hERα66 in MCF7 Breast Cancer Cells. Endocrinology 2005, 146, 5474–5484.
  21. Maczis, M.A.; Maceyka, M.; Waters, M.R.; Newton, J.; Singh, M.; Rigsby, M.F.; Turner, T.; Alzubi, M.A.; Harrell, J.C.; Milstien, S.; et al. Sphingosine kinase 1 activation by estrogen receptor α36 contributes to tamoxifen resistance in breast cancer. J. Lipid Res. 2018, 59, 2297–2307.
  22. Zhang, X.; Cao, J.; Wang, Z. ER-α46, a variant of ER-α, is expressed in human breast carcinoma and enhances estrogen sensitivity in breast cancer cells. Cancer Res. 2007, 67, 986.
  23. Gu, W.; Dong, N.; Wang, P.; Shi, C.; Yang, J.; Wang, J. Tamoxifen resistance and metastasis of human breast cancer cells were mediated by the membrane-associated estrogen receptor ER-α36 signaling in vitro. Cell Biol. Toxicol. 2016, 33, 183–195.
  24. Prossnitz, E.R.; Barton, M. The G-protein-coupled estrogen receptor GPER in health and disease. Nat. Rev. Endocrinol. 2011, 7, 715–726.
  25. Tan, S.; Ding, K.; Chong, Q.-Y.; Zhao, J.; Liu, Y.; Shao, Y.; Zhang, Y.; Yu, Q.; Xiong, Z.; Zhang, W.; et al. Post-transcriptional regulation of ERBB2 by miR26a/b and HuR confers resistance to tamoxifen in estrogen receptor-positive breast cancer cells. J. Biol. Chem. 2017, 292, 13551–13564.
  26. Choi, H.-J.; Joo, H.-S.; Won, H.-Y.; Min, K.-W.; Kim, H.-Y.; Son, T.; Oh, Y.-H.; Lee, J.-Y.; Kong, G. Role of RBP2-Induced ER and IGF1R-ErbB Signaling in Tamoxifen Resistance in Breast Cancer. J. Natl. Cancer Inst. 2017, 110, 400–410.
  27. Xu, S.; Ge, J.; Zhang, Z.; Zhou, W. MiR-129 inhibits cell proliferation and metastasis by targeting ETS1 via PI3K/AKT/mTOR pathway in prostate cancer. Biomed. Pharmacother. 2017, 96, 634–641.
  28. Augereau, P.; Patsouris, A.; Bourbouloux, E.; Gourmelon, C.; Lacourtoisie, S.A.; Rigaud, D.B.; Soulié, P.; Frenel, J.-S.; Campone, M. Hormonoresistance in advanced breast cancer: A new revolution in endocrine therapy. Ther. Adv. Med. Oncol. 2017, 9, 335–346.
  29. Lu, S.; Du, Y.; Cui, F.; Feng, X.; Ma, Y.; Liu, H. Downregulation of BAG-1 in T47D cells promotes resistance to tamoxifen via activation of the PI3K/Akt/mTOR signaling pathway. Oncol. Rep. 2019, 41, 1901–1910.
  30. The FANTOM Consortium; Carninci, P.; Kasukawa, T.; Katayama, S.; Gough, J.; Frith, M.; Maeda, N.; Oyama, R.; Ravasi, T.; Lenhard, B.; et al. The Transcriptional Landscape of the Mammalian Genome. Science 2005, 309, 1559–1563.
  31. Guttman, M.; Amit, I.; Garber, M.; French, C.; Lin, M.F.; Feldser, D.; Huarte, M.; Zuk, O.; Carey, B.W.; Cassady, J.P.; et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nat. Cell Biol. 2009, 458, 223–227.
  32. Djebali, S.; Davis, C.A.; Merkel, A.; Dobin, A.; Lassmann, T.; Mortazavi, A.; Tanzer, A.; Lagarde, J.; Lin, W.; Schlesinger, F.; et al. Landscape of transcription in human cells. Nat. Cell Biol. 2012, 489, 101–108.
  33. Mercer, T.; Gerhardt, D.J.; Dinger, M.; Crawford, J.; Trapnell, C.; A Jeddeloh, J.; Mattick, J.; Rinn, J.L. Targeted RNA sequencing reveals the deep complexity of the human transcriptome. Nat. Biotechnol. 2011, 30, 99–104.
  34. Hangauer, M.J.; Vaughn, I.W.; McManus, M.T. Pervasive Transcription of the Human Genome Produces Thousands of Previously Unidentified Long Intergenic Noncoding RNAs. PLoS Genet. 2013, 9, e1003569.
  35. Antonov, I.V.; Mazurov, E.; Borodovsky, M.; A Medvedeva, Y. Prediction of lncRNAs and their interactions with nucleic acids: Benchmarking bioinformatics tools. Brief. Bioinform. 2018, 20, 551–564.
  36. Kasinski, A.; Slack, F.J. MicroRNAs en route to the clinic: Progress in validating and targeting microRNAs for cancer therapy. Nat. Rev. Cancer 2011, 11, 849–864.
  37. Ma, J.; Dong, C.; Ji, C. MicroRNA and drug resistance. Cancer Gene Ther. 2010, 17, 523–531.
  38. Mulrane, L.; McGee, S.F.; Gallagher, W.M.; O’Connor, D.P. miRNA Dysregulation in Breast Cancer. Cancer Res. 2013, 73, 6554–6562.
  39. Ahmad, A.; Ginnebaugh, K.R.; Yin, S.; Bollig-Fischer, A.; Reddy, K.B.; Sarkar, F.H. Functional role of miR-10b in tamoxifen resistance of ER-positive breast cancer cells through down-regulation of HDAC. BMC Cancer 2015, 15, 1–10.
  40. Cui, J.; Yang, Y.; Li, H.; Leng, Y.; Qian, K.; Huang, Q.; Zhang, C.; Lu, Z.; Chen, J.; Sun, T.; et al. MiR-873 regulates ERα transcriptional activity and tamoxifen resistance via targeting CDK3 in breast cancer cells. Oncogene 2014, 34, 3895–3907.
  41. Yu, X.; Luo, A.; Liu, Y.; Wang, S.; Li, Y.; Shi, W.; Liu, Z.; Qu, X. MiR-214 increases the sensitivity of breast cancer cells to tamoxifen and fulvestrant through inhibition of autophagy. Mol. Cancer 2015, 14, 1–16.
  42. Zhu, J.; Zou, Z.; Nie, P.; Kou, X.; Wu, B.; Wang, S.; Song, Z.; He, J. Downregulation of microRNA-27b-3p enhances tamoxifen resistance in breast cancer by increasing NR5A2 and CREB1 expression. Cell Death Dis. 2016, 7, e2454.
  43. Chen, M.-J.; Cheng, Y.-M.; Chen, C.-C.; Chen, Y.-C.; Shen, C.-J. MiR-148a and miR-152 reduce tamoxifen resistance in ER+ breast cancer via downregulating ALCAM. Biochem. Biophys. Res. Commun. 2017, 483, 840–846.
  44. Guttman, M.; Russell, P.; Ingolia, N.T.; Weissman, J.S.; Lander, E.S. Ribosome Profiling Provides Evidence that Large Noncoding RNAs Do Not Encode Proteins. Cell 2013, 154, 240–251.
  45. Gil, N.; Ulitsky, I. Regulation of gene expression by cis-acting long non-coding RNAs. Nat. Rev. Genet. 2019, 21, 102–117.
  46. Derrien, T.; Johnson, R.; Bussotti, G.; Tanzer, A.; Djebali, S.; Tilgner, H.; Guernec, G.; Martin, D.; Merkel, A.; Knowles, D.G.; et al. The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression. Genome Res. 2012, 22, 1775–1789.
  47. Wu, P.; Mo, Y.; Peng, M.; Tang, T.; Zhong, Y.; Deng, X.; Xiong, F.; Guo, C.; Wu, X.; Li, Y.; et al. Emerging role of tumor-related functional peptides encoded by lncRNA and circRNA. Mol. Cancer 2020, 19, 1–14.
  48. Lyle, R.; Watanabe, D.; Vruchte, D.T.; Lerchner, W.; Smrzka, O.W.; Wutz, A.; Schageman, J.; Hahner, L.; Davies, C.; Barlow, D.P. The imprinted antisense RNA at the Igf2r locus overlaps but does not imprint Mas. Nat. Genet. 2000, 25, 19–21.
  49. Rinn, J.; Kertesz, M.; Wang, J.; Squazzo, S.L.; Xu, X.; Brugmann, S.A.; Goodnough, L.H.; Helms, J.A.; Farnham, P.; Segal, E.; et al. Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs. Cell 2007, 129, 1311–1323.
  50. Mercer, T.; Dinger, M.; Sunkin, S.M.; Mehler, M.F.; Mattick, J. Specific expression of long noncoding RNAs in the mouse brain. Proc. Natl. Acad. Sci. USA 2008, 105, 716–721.
  51. Hung, T.; Wang, Y.; Lin, M.F.; Koegel, A.K.; Kotake, Y.; Grant, G.; Horlings, H.M.; Shah, N.; Umbricht, C.; Wang, P.; et al. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat. Genet. 2011, 43, 621–629.
  52. Li, J.; Tian, H.; Yang, J.; Gong, Z. Long Noncoding RNAs Regulate Cell Growth, Proliferation, and Apoptosis. DNA Cell Biol. 2016, 35, 459–470.
  53. Huarte, M.; Guttman, M.; Feldser, D.; Garber, M.; Koziol, M.; Kenzelmann-Broz, D.; Khalil, A.M.; Zuk, O.; Amit, I.; Rabani, M.; et al. A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response. Cell 2010, 142, 409–419.
  54. Latos, P.A.; Pauler, F.M.; Koerner, M.V.; Şenergin, H.B.; Hudson, Q.; Stocsits, R.R.; Allhoff, W.; Stricker, S.; Klement, R.M.; Warczok, K.E.; et al. Airn Transcriptional Overlap, But Not Its lncRNA Products, Induces Imprinted Igf2r Silencing. Science 2012, 338, 1469–1472.
  55. Santoro, F.; Mayer, D.; Klement, R.M.; Warczok, K.E.; Stukalov, A.; Barlow, D.P.; Pauler, F.M. Imprinted Igf2r silencing depends on continuous Airn lncRNA expression and is not restricted to a developmental window. Development 2013, 140, 1184–1195.
  56. Guttman, M.; Donaghey, J.; Carey, B.W.; Garber, M.; Grenier, J.K.; Munson, G.; Young, G.; Lucas, A.B.; Ach, R.; Bruhn, L.; et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nat. Cell Biol. 2011, 477, 295–300.
  57. Ng, S.-Y.; Johnson, R.; Stanton, L.W. Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors. EMBO J. 2011, 31, 522–533.
  58. Lin, N.; Chang, K.-Y.; Li, Z.; Gates, K.; Rana, Z.A.; Dang, J.; Zhang, D.; Han, T.; Yang, C.-S.; Cunningham, T.; et al. An Evolutionarily Conserved Long Noncoding RNA TUNA Controls Pluripotency and Neural Lineage Commitment. Mol. Cell 2014, 53, 1005–1019.
  59. Yu, C.-Y.; Kuo, H.-C. The Trans-Spliced Long Noncoding RNA tsRMSTImpedes Human Embryonic Stem Cell Differentiation Through WNT5A-Mediated Inhibition of the Epithelial-to-Mesenchymal Transition. Stem Cells 2016, 34, 2052–2062.
  60. Obaid, M.; Udden, S.M.N.; Deb, P.; Shihabeddin, N.; Zaki, H.; Mandal, S.S. LncRNA HOTAIR regulates lipopolysaccharide-induced cytokine expression and inflammatory response in macrophages. Sci. Rep. 2018, 8, 1–18.
  61. 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.; et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nat. Cell Biol. 2010, 464, 1071–1076.
  62. Huang, R.; Wang, X.; Zhang, W.; Zhangyuan, G.; Jin, K.; Yu, W.; Xie, Y.; Xu, X.; Wang, H.; Sun, B. Down-Regulation of LncRNA DGCR5 Correlates with Poor Prognosis in Hepatocellular Carcinoma. Cell. Physiol. Biochem. 2016, 40, 707–715.
  63. Schmidt, K.; Joyce, C.E.; Buquicchio, F.; Brown, A.; Ritz, J.; Distel, R.J.; Yoon, C.H.; Novina, C.D. The lncRNA SLNCR1 Mediates Melanoma Invasion through a Conserved SRA1-like Region. Cell Rep. 2016, 15, 2025–2037.
  64. de Oliveira, J.C.; Oliveira, L.C.; Mathias, C.; Pedroso, G.A.; Lemos, D.S.; Salviano-Silva, A.; Jucoski, T.S.; Lobo-Alves, S.C.; Zambalde, E.P.; Cipolla, G.A.; et al. Long non-coding RNAs in cancer: Another layer of complexity. J. Gene Med. 2019, 21, e3065.
  65. Huang, L.; Liang, G.; Zhang, Q.; Zhao, W. The Role of Long Noncoding RNAs in Antiestrogen Resistance in Breast Cancer: An Overview and Update. J. Breast Cancer 2020, 23, 129–140.
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