Long non‑coding RNA PCAT6 regulates bladder cancer progression via the microRNA‑143‑3p/PDIA6 axis

Abstract

Although long non-coding (lnc)RNAs have been reported to be involved in the pathological development of bladder cancer, the functions of lncRNA prostate cancer-associated transcript 6 (PCAT6) and its underlying mechanism of action in bladder cancer remain unknown. The present study aimed to investigate the effect of PCAT6 in bladder cancer progression and explore its potential application as a novel treatment target. The expression of PCAT6 and miR-143-3p in bladder cancer tissues, adjacent normal tissues and cell lines was measured using reverse transcription-quantitative PCR. Fluorescence in situ hybridization assay was used to detect the subcellular localization of PCAT6. MTT, EdU, Transwell and wound healing assays were conducted to assess the biological function of PCAT6 on cell proliferation, migration and invasion. Putative binding sites between miR-143-3p and PCAT6 or PDIA6 were predicted using starBase, Lncbase and TargetScan analyzes. Dual-luciferase reporter assay was also used to confirm the potential binding between PCAT6 and miR-143-3p. RNA immunoprecipitation assay was performed to verify the possible interaction between PCAT6 and miR-143-3p. Western blotting was used to measure the expression of PDIA6. The results demonstrated that the expression levels of PCAT6 were upregulated in bladder cancer tissues relative to those in adjacent normal bladder tissues. Knockdown of PCAT6 served a role in suppressing the proliferation, migration and invasion of T24T and EJ bladder cancer cells. PCAT6 knockdown contributed to a reduction of PDIA6 expression at the mRNA and protein levels compared with that in negative control-transfected cells, whilst the miR-143-3p inhibitor partially mitigated this reduction effect. In addition, rescue experiments revealed that the miR-143-3p inhibitors reversed the effects of PCAT6 silencing on the malignant phenotypes of bladder cancer. Collectively, the results of the present study demonstrated that PCAT6 may serve an oncogenic role in bladder cancer via the miR-143-3p/PDIA6 axis. These results may provide a potential therapeutic target for the treatment of bladder cancer.

An Unfolded Protein Response Related Signature Could Robustly Predict Survival Outcomes and Closely Correlate With Response to Immunotherapy and Chemotherapy in Bladder Cancer

“…Cheng once demonstrated that PDIA6 downregulation inhibited BC cell proliferation and invasion via the Wnt/β-catenin signaling pathway ( Cheng et al, 2017 ). Meanwhile, Zhang discovered that lncRNA PCAT6 could regulate BC progression via the microRNA-143-3p/PDIA6 axis ( Zhang et al, 2021d ). Furthermore, POP4, PREB, SRPRB, TATDN2, YIF1A, and ZBTB17 were seldom studied in BC and perhaps researchers need to pay more attention to them in the future.…”

MIR100HG Regulates CALD1 Gene Expression by Targeting miR-142-5p to Affect the Progression of Bladder Cancer Cells in vitro, as Revealed by Transcriptome Sequencing

“…A large number of abnormally expressed lncRNAs have been detected in bladder cancer that affect the occurrence, proliferation and migration of bladder cancer cells. For example, Zhang et al reported that the lncRNA PCAT6 regulates the proliferation and migration of bladder cancer through the miR-143-3p/PDIA6 axis (Zhang et al, 2021). In addition, Chen et al found that the lncRNA LNC-LBCS inhibits the self-renewal and chemotherapy resistance of bladder cancer stem cells through the epigenetic silencing of SOX2 (Chen et al, 2019).…”

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.…”

“…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 [ 25 ], GIST [ 32 ], GBM [ 35 ], Osa [ 44 , 45 ], PA [ 50 ], and Pca [ 52 ] cells. Cytoplasmic lncRNAs regulate genes at the translational and post-transcriptional levels, such as interaction with cytoplasmic proteins [ 58 ], and interaction with microRNAs to regulate downstream mRNA levels [ 59 , 60 , 61 , 62 , 63 ].…”

“…The inhibition of miR-513a partially offsets the proliferation, migration, and invasion induced by the knockdown of PCAT6 [ 21 ]. Moreover, PCAT6 promotes cell proliferation, migration, and invasion by inhibiting miR-143-3p and upregulating protein disulfide isomerase familyA mumber 6 (PDIA6), in BC [ 25 ]. In NSCLC PCAT6 absorbs miR-330-5p and promotes cell proliferation, migration, invasion in vitro, and tumor growth in vivo [ 39 ].…”