lncRNA PCAT6 facilitates cell proliferation and invasion via regulating the miR‑326/hnRNPA2B1 axis in liver cancer

Abstract

Liver cancer is one of the most common malignant human tumors with the highest morbidity and mortality rates of all cancer types in China. Evidence suggests that long non-coding RNA prostate cancer-associated transcript 6 (PCAT6) plays an essential role in tumor progression. However, the roles and mechanism of PCAT6 in liver cancer remain unclear. The present study showed that the expression of PCAT6 and heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) was upregulated in liver cancer tissues compared with non-cancerous tissues and were associated with poor overall survival time, whereas microRNA (miR)-326 expression was downregulated. Moreover, knockdown of PCAT6 significantly inhibited the proliferation and invasion of liver cancer cells in vitro and in vivo. A dual-luciferase reporter gene assay demonstrated that PCAT6 could bind to miR-326 and that hnRNPA2B1 was a direct target gene of miR-326. Mechanistically, silenced PCAT6 suppressed the malignant phenotype of liver cancer cells through upregulating the inhibitory effect of miR-326 on hnRNPA2B1 expression. Taken together, these data demonstrated that knockdown of PCAT6 inhibited liver cancer progression through regulation of the miR-326/hnRNPA2B1 axis, suggesting that PCAT6 functions as an oncogene and may be a useful biomarker for the future diagnosis and treatment of liver cancer.

Alternative Splicing, Epigenetic Modifications and Cancer: A Dangerous Triangle, or a Hopeful One?

“…Prostate cancer-associated transcript 6 (PCAT6) is a lncRNA that sponges miR-326, an inhibitor of hnRNPA2B1 expression. PCAT6 is overexpressed in hepatocellular carcinoma and, consequently, the miR-326 level is reduced and that of hnRNPA2B1 enhanced [106], but the exact AS events effected have not yet been determined.…”

PCAT6 May Be a Whistler and Checkpoint Target for Precision Therapy in Human 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) [ 21 , 24 , 25 ], breast cancer (BrCa) [ 26 , 27 ], cervical cancer (CC) [ 28 , 29 ], colorectal cancer (CRC) [ 30 , 31 ], gastrointestinal stromal tumor (GIST) [ 32 ], gastric cancer (GC) [ 33 , 34 ], glioblastoma (GBM) [ 35 ], hepatocellular carcinoma (HCC) [ 36 , 37 , 38 ], lung cancer (LC) [ 20 , 39 , 40 , 41 , 42 , 43 ], osteosarcoma (Osa) [ 44 , 45 , 46 ], ovarian cancer (OvCa) [ 47 , 48 ], cholangiocarcinoma (CCA) [ 49 ], pituitary adenoma (PA) [ 50 ], pancreatic ductal adenocarcinoma (PDAC) [ 51 ], and prostate cancer (PCa) [ 52 , 53 ]. 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.…”

“…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 ) [ 26 , 29 , 30 , 38 , 39 , 40 , 43 , 44 , 46 , 50 , 52 , 53 , 54 ]. 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 [ 55 ].…”

“…Furthermore, PCAT6 , transcriptionally activated by YY1, promoted the proliferation and prevented the apoptosis of GBM cells through the PCAT6 /miR-513/IGF2BP1 positive loop [ 35 ]. PCAT6 promotes HCC cell proliferation and invasion in vitro, and tumor growth in vivo by attenuating miR-326 and upregulating heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) [ 38 ]. Moreover, enzalutamide induced PCAT6 also promotes PCa cell proliferation, metastasis, and neuroendocrine differentiation (NED) via the miR-326/HNRNPA2B1 axis in vitro or in vivo [ 52 ].…”

“…Subsequently, univariate analysis and multivariate analysis also have revealed that high expression of PCAT6 is an independent poor prognostic factor for both OS and DFS in CC [ 28 ]. For HCC, many reports have revealed that upregulated PCAT6 is associated with shorter OS, PFS, and DFS [ 36 , 37 , 38 , 132 ]. Similarly, Kaplan–Meier Plotter analyses have demonstrated that high expression of PCAT6 can be used as a prognostic biomarker for OS, PFS, and post-progression survival (PPS) in OvCa patients [ 48 ].…”