The Cancer-Testis Long Non-coding RNA PCAT6 Facilitates the Malignant Phenotype of Ovarian Cancer by Sponging miR-143-3p
Open Access
- 4 February 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Cell and Developmental Biology
Abstract
Background: It has been reported that long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis. However, their roles in ovarian cancer (OC) remain to be elucidated. The aim of this study was to uncover the function and underlying mechanisms of PCAT6 in OC. Methods: The expression pattern of PCAT6 in OC was analyzed in the GSE137238, GSE143897 and Gene Expression Profile Interactive Analysis (GEPIA) datasets. Kaplan–Meier Plotter online software was used for survival analysis. Loss-of-function assays and gain-of-function assays were used to assess the function of PCAT6 in OC development. Moreover, small-RNA sequencing, bioinformatic analysis, luciferase assays and rescue experiments were carried out to clarify the potential mechanism of PCAT6 in OC. Results: PCAT6 expression was significantly increased in OC tissues and positively correlated with advanced stages and with poor overall survival, progression-free survival and post-progression survival. Knockdown of PCAT6 in A2780 and SKOV3 cells inhibited OC cell proliferation, migration and invasion. In contrast, Overexpression of PCAT6 exerted the opposite effects on OC cells. Notably, PCAT6 bound to miR-143-3p and affected the expression of transforming growth factor (TGF)-β-activated kinase 1 (TAK1). Subsequent rescue assays confirmed that upregulation of miR-143-3p decreased the PCAT6 overexpression-induced promotion of proliferation, migration and invasion. Moreover, downregulation of miR-143-3p reversed the PCAT6 knockdown-induced inhibition of proliferation, migration, and invasion. Conclusions: Our findings demonstrate that PCAT6 plays an oncogenic role in OC and may be useful as a therapeutic target for OC.This publication has 33 references indexed in Scilit:
- Role of lncRNAs in ovarian cancer: defining new biomarkers for therapeutic purposesDrug Discovery Today, 2018
- MiR-143-3p suppresses the progression of ovarian cancer2018
- MiR-143 Targeting TAK1 Attenuates Pancreatic Ductal Adenocarcinoma Progression via MAPK and NF-κB Pathway In VitroDigestive Diseases and Sciences, 2017
- Knockdown of Long Noncoding RNA PCAT6 Inhibits Proliferation and Invasion in Lung Cancer CellsOncology Research, 2016
- RETRACTED ARTICLE: MiR-143-3p functions as a tumor suppressor by regulating cell proliferation, invasion and epithelial–mesenchymal transition by targeting QKI-5 in esophageal squamous cell carcinomaMolecular Cancer, 2016
- Systematic identification of genes with a cancer-testis expression pattern in 19 cancer typesNature Communications, 2016
- Elevated TAK1 augments tumor growth and metastatic capacities of ovarian cancer cells through activation of NF-κB signalingOncotarget, 2014
- MicroRNA-143 functions as a tumor suppressor in human bladder cancer T24 cellsCancer Letters, 2011
- Regulation of the immune response by stress‐activated protein kinasesImmunological Reviews, 2009
- TAK1 is required for TGF-β1-mediated regulation of matrix metalloproteinase-9 and metastasisOncogene, 2007