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Expression and Subcellular Localization of PCAT6
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This entry is adapted from the peer-reviewed paper 10.3390/cancers13236101

Prostate cancer-associated transcript 6 (PCAT6), as a newly discovered carcinogenic long non-coding RNA (lncRNA), is abnormally expressed in multiple diseases. PCAT6 is also named KDM5B-AS1, KDM5BAS1, PCAN-R1, ncRNA-a2, or onco-lncRNA-96. It was first described as ncRNA-a2 in 2010. The gene of PCAT6 is located on chromosome 1q32.1 and contains two exons. It consists of 968 bp and has two transcript variants: transcript variant 1 (NR_046325.1) and transcript variant 2 (NR_046326.1).

lncRNA PCAT6 Expression Subcellular Localization

1. The Abnormal Expression of PCAT6 in Cancers

The expression of PCAT6 is found to be aberrantly elevated in various human tumor tissues and cell lines compared with matched normal ones, including bladder cancer (BC) [1][2][3], breast cancer (BrCa) [4][5], cervical cancer (CC) [6][7], colorectal cancer (CRC) [8][9], gastrointestinal stromal tumor (GIST) [10], gastric cancer (GC) [11][12], glioblastoma (GBM) [13], hepatocellular carcinoma (HCC) [14][15][16], lung cancer (LC) [17][18][19][20][21][22], osteosarcoma (Osa) [23][24][25], ovarian cancer (OvCa) [26][27], cholangiocarcinoma (CCA) [28], pituitary adenoma (PA) [29], pancreatic ductal adenocarcinoma (PDAC) [30], and prostate cancer (PCa) [31][32]. In subsequent experiments on the biological functions of tumor cells, it has been revealed that a high level of PCAT6 has strong cancer-promoting effects, mainly including the promotion of cell proliferation, enhancement of migration, invasion and EMT process, as well as the inhibition of cell apoptosis. Meanwhile, PCAT6 has been shown to promote tumor growth and metastasis in xenograft mouse models (Table 1) [4][7][8][16][18][19][22][23][25][29][31][32][33]. However, Amelia et al. reported that the expression level of PCAT6 was opposite in lung tumor tissues and lung cancer cell lines compared with the normal control group [34]. Compared with paired normal tissue, PCAT6 expression level is higher in lung tumors, while its level is lower in non-small cell lung cancer (NSCLC) cell lines compared to the normal human fetal lung fibroblast cell line (IMR-90) [34]. Interestingly, Tu et al. found that, compared to T cells, B cells, dendritics, and neutrophils, PCAT6 expression was the highest in macrophages which derived from patients of CCA, especially M2 macrophages [33]. Furthermoer, PCAT6 expression level is also significantly higher in the blood samples of some cancer patients, including BC [2] and LC [20][35]. Contradictorily, Siddique et al., testified that PCAT6 level had no significant difference in the blood between Saudi CRC patients and healthy donors [36]. It is speculated that the cause of this result may be ethnically related, and the expression level of PCAT6 in CRC patients of different races might be different.
Table 1. Functional characterization of PCAT6 in multiple human cancers.
Table
Tumor Types Expression Sample Type Role Functional Role in Vitro Functional Role in Vivo Related Genes/Protein/Pathways Ref.
Bladder cancer Up cells (RT4, T24, J82, UMUC3, 5637), patient tissue and serum Tumor promoter Cell proliferation and apoptosis   NA [2]
Up Cells (T24, EJ, 253j, 5637), patient tissue Tumor promoter Cell proliferation, migration, and invasion   miR-513a-5p [1]
Up Cells (T24T, EJ, UMUC3, 5637), patient tissue Tumor promoter Cell proliferation, migration, and invasion   miR-143-3p, PDIA6 [3]
Breast cancer Up Cells (MDA-MB-231, MDA-MB-468, MDA-MB-436, HCC-1937), patient tissue Tumor promoter Cell proliferation, migration, invasion, EMT process, and angiogenesis Tumor growth, metastasis, and angiogenesis VEGF, VEGFR2/Akt/mTOR, miR-4723-5p, USP14, E-cadherin, N-cadherin, Slug, Twist, [4]
Up Cells (MDA-MB-468, MDA-MB-231), patient tissue Tumor promoter Cell proliferation, apoptosis, cell cycle, and radiosensitivity   miR-185-5p, TPD52 [5]
Cervical cancer Up Cells (Caski, SW756, HeLa, ME-180, SiHa, C33A), patient tissue Tumor promoter Cell proliferation, apoptosis, migration, and invasion   Wnt/β-catenin, β-catenin, cyclin D1, c-myc [6]
Up Cells (SiHa, HeLa, ME180, C-33A), patient tissue Tumor promoter Cell proliferation, apoptosis, migration, invasion, and chemoresistance Tumor growth miR-543, Bcl-2, cleaved-caspase 3, ZEB1 [7]
Colorectal cancer Up Cells (SW628, SW480, RKO, COLO320HSR, HCT116), patient tissue Tumor promoter Cell proliferation and apoptosis Tumor growth Cleaved-caspase 3, ARC, EZH2 [8]
Up Cells (HCT116, HT-29, SW620, SW480, DLD-1, RKO, LoVo), patient tissue Tumor promoter Cell proliferation and chemoresistance   miR-204, HMGA2, PI3K, Akt [9]
Gastrointestinal stromal tumor Up Cells (GIST-H1, GIST-882, GIST-T1, GIST-48), patient tissue Tumor promoter Cell proliferation, stemness, and apoptosis   Wnt/β-catenin, miR-143-3p, PRDX5 [10]
Gastric cancer Up Cells (BGC-823, SGC-7901, HGC-27, MKN45), patient tissue Tumor promoter Cell proliferation, migration, EMT, and apoptosis   miR-30, MKRN3, caspase 3, caspase 9, Bax, Bcl-2, E-cadherin, N-cadherin, Vimentin, ZEB1, Snail [12]
Up Cells (MKN45, SGC-7901, AGS, MKN28), patient tissue Tumor promoter Cell proliferation, EMT, and apoptosis   Cyclin D1, p53, Bax, cleaved caspase 3, E-cadherin, N-cadherin, Vimentin, Snail, ZEB1, miR-15a, RB/E2F, Wnt/β-catenin [11]
Glioblastoma Up Cells (A172, U251, U87, LN229), patient tissue Tumor promoter Cell proliferation and apoptosis   YY1, miR-513, IGF2BP1, Akt [13]
Hepatocellular carcinoma Up Patient tissue Tumor promoter Cell proliferation and migration   NA [14]
Up Cells (HuH7, SMMC-7721, Hep3B, HepG2, PLC/PRF/5), patient tissue Tumor promoter Cell proliferation, cycle, apoptosis, and migration   PCNA, CCND1, Bcl-2 [15]
Up Cells (MHCC97H, HepG2, Huh7), patient tissue Tumor promoter Cell proliferation and invasion Tumor growth miR-326, hnRNPA2B1 [16]
Lung cancer Up Cells (H1650, HCC827, H1975, A549), patient tissue Tumor promoter Cell proliferation, migration, and invasion, Tumor growth miR-330-5p [18]
Up Cells (SK-MES-1, H1703, H520, H1299, H1975, SPCA1, A549), patient tissue Tumor promoter Cell proliferation, cycle, apoptosis, migration, and invasion Tumor growth EZH2, LATS2 [19]
Up Cells (H292, PC-9, CL1-5, H460, H1650, A549, H446, H1975) Tumor promoter Cell proliferation, apoptosis, and invasion   Bcl-2, Bax, c-myc, p53 [17]
Up Cells (H446, H1975), patient tissue Tumor promoter Cell proliferation, migration, invasion, and apoptosis   c-myc, MMP9, cleaved-caspase-3, Wnt5a, β-catenin. miR-326. [21]
Up Cells (H1838, H522, H2228, H358, H1299, A549), Tumor promoter Cell proliferation, migration, invasion, cycle, apoptosis Tumor growth Caspase-3, Ki-67 [22]
Osteosarcoma Up Cells (MG-63, Saos-2, 143B, U2OS), patient tissue Tumor promoter Cell proliferation, migration, invasion, and cell cycle Tumor growth ZEB1, miR-143-3p [23]
Up Cells (Saos2, MG63, U2OS, HOS) Tumor promoter Cell proliferation, migration, and invasion Tumor growth MMP2, MMP9, p53, p21, MDM2 [25]
Up Cells (Saos2, HOS, U2OS, 143B, KHOS/240S, MG63, SK-ES-1), patient tissue Tumor promoter Cell proliferation, migration, and invasion   miR-185-5p, TGF-β, p-SMAD, TGFBR1/2 [24]
Ovarian cancer Up Cells (OVCAR3, PEO1, A2780, 3AO, CAOV3, SKOV3), patient tissue Tumor promoter Cell proliferation, migration, and invasion   PTEN [26]
Up Patient tissue Tumor promoter Cell proliferation, migration, and invasion   miR-143-3p, TAK1 [27]
Cholangiocarcinoma Up Patient-derived macrophages, patient tissue Tumor promoter M2 polarization of macrophages, cellular reactive oxygen species production, mitochondrial and metabolic dysfunction Tumor growth miR-326, RhoA, ROCK1, ROCK2 [33]
Up Cell (ICC-9810, CCLP1, HuCC-T1, QBC939), patient tissue Tumor promoter Cell proliferation and invasion   miR-330-5p [28]
Pituitary adenomas Up Patient tissue Tumor promoter Cell proliferation, migration, invasion, viability, apoptosis, cell cycle, and EMT Tumor growth, apoptosis, EMT miR-139-3p, BRD4, E-cadherin, N-cadherin, Bcl-2, Bax, cleaved-caspase 3 [29]
Pancreatic ductal adenocarcinoma Up Cell (Capan-2, AsPC-1, PANC1, BxPC-3), Patient tissue Tumor promoter Cell proliferation, migration, and invasion   miR-185-5p, CBX2 [30]
Prostate cancer Up Cell (NCI-H660), patient tissue Tumor promoter Cell NED, proliferation, and invasion Tumor growth and metastasis NSE, SYP, ChgA, miR-326, hnRNPA2B1 [31]
Up Patient tissue Tumor promoter Cell proliferation, cycle, migration, and invasion Tumor growth and BM IGF2BP2, IGF1R, PI3K/Akt, NF-κB, METTL3, ALKBH5 [32]
PDIA6, protein disulfide isomerase family A number 6; EMT, epithelial-mesenchymal transition; VEGF, vascular endothelial growth factor; VEFGR2, vascular endothelial growth factor receptor 2; Akt, serine/threonine kinase; mTOR, mammalian target of rapamycin; USP14, ubiquitin-specific protease-14; TPD52, tumor protein D52; Bcl-2, B-cell lymphoma-2; ZEB1, zinc finger E-box binding homeobox 1; ARC, activity regulated cytoskeleton associated protein; EZH2, enhancer of zeste homolog 2; HMGA2, high mobility group AT-hook 2; PRDX5, peroxiredoxin 5; MKRN3, makorin ring finger protein 3; YY1, Yin Yang 1; IGF2BP1, insulin like growth factor 2 mRNA binding protein 1; IGF2BP2, insulin like growth factor 2 mRNA binding protein 2; PCNA, proliferating cell nuclear antigen; CCND1, cyclin D1; hnRNPA2B1, heterogeneous nuclear ribonucleoprotein A2/B1, LATS2, large tumor suppressor kinase 2; Bax, BCL2 associated X; MMP2, matrix metallopeptidase 2; MMP9, matrix metallopeptidase 9; MDM2, mouse double minute 2 homolog; TGF-β, transforming growth factor β; TGFBR1/2, transforming growth factor β receptor 1/2; PTEN, phosphatase and tensin homolog; TAK1, TGF-β activated kinase 1; RhoA, ras homolog family member A; ROCK1/2, Rho associated coiled-coil containing protein kinase 1/2; BRD4, bromodomain containing 4; CBX2, chromobox 2; NED, neuroendocrine differentiation; SYP, synaptophysin; ChgA, chromogranin A; BM, bone metastasis; IGF1R, insulin like growth factor 1 receptor; METTL3, methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit; ALKBH5, alkB homolog 5.

2. The Subcellular Localization of PCAT6 in Cancer Cell Lines

LncRNAs play diverse functions depending on different subcellular or extracellular compartmental localizations. Most studies indicate that PCAT6 is primarily located in the cytoplasm of BC [3], GIST [10], GBM [13], Osa [23][24], PA [29], and Pca [31] cells. Cytoplasmic lncRNAs regulate genes at the translational and post-transcriptional levels, such as interaction with cytoplasmic proteins [37], and interaction with microRNAs to regulate downstream mRNA levels [38][39][40][41][42]. Shi et al. determined that PCAT6 was principally distributed in the nucleus of NSCLC cells [19]. Nucleic lncRNAs regulate genes at the epigenetic and transcriptional levels, including histone modifications [43][44], DNA methylation [45], and chromatin remodeling [46]. Furthermore, Dong and Lang et al. demonstrated that PCAT6 was located in both the cytoplasm and nucleus of BrCa and PCa cells by fluorescence in situ hybridization (FISH) and subcellular fraction assays, which was different from most studies [4][32]. This is similar to the lncRNA HOTAIR, which regulates genes at both the epigenetic and transcriptional levels, as well as at the post-transcriptional level [47].

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