LINC00494 Promotes Ovarian Cancer Development and Progression by Modulating NFκB1 and FBXO32.

Yang Shu,Jinqiu Li,Yanhong Shan,He Zhang

doi:10.3389/fonc.2020.541410

Abstract

BackgroundOvarian cancer represents one of the most frequent gynecological cancers and is significant cause of death for women around the world. Long non-coding RNAs (lncRNAs) are recognized as critical governors of gene expression during carcinogenesis, but their effects on the occurrence and development of ovarian cancer require further investigation. In this report, we characterized LINC00494 as a novel oncogenic lncRNA in ovarian cancer.MethodsBioinformatics analysis predicted potential interactions among LINC00494, NFκB1, and FBXO32 in ovarian cancer, which were tested by dual-luciferase reporter assay, RNA pull-down, RIP, and ChIP assay. Cancer cells were transfected with relevant treated plasmids, followed by scratch and Transwell assays. The treated cells were injected into nude mice to establish a xenograft model for testing effects of LINC00494 and its target gene in vivo.ResultsLINC00494 and NFκB1 were highly expressed whereas FBXO32 had low expression in ovarian cancer cells and tissues. LINC00494 was found to bind NFκB1 and increase its activity, while NFκB1 was enriched at the FBXO32 promoter region, where it acted to reduce FBXO32 transcription. Overexpression of LINC00494 elevated NFκB1 expression and enhanced cell migration, invasion and tumorigenesis, but additional overexpression of FBXO32 interfered with the tumorgenicity of ovarian cancer cells in vitro and in vivo.ConclusionOur work demonstrated that LINC00494 promoted ovarian cancer progression by modulating FBXO32 via binding with the transcription factor NFκB1. These results provided new insight into the mechanism of ovarian cancer pathogenesis and suggested new therapeutic targets.

Highlights

Ovarian cancer is one of the most frequently occurring gynecological cancers, and brings high mortality and morbidity to women the world over [1]
We predicted through the LncMAP database that NFkB1 was a putative transcriptional factor regulated by LINC00494, and that FBXO32 was the downstream target gene of NFkB1
FBXO32 (F-box protein 32) is a novel TGF-beta/SMAD4 target gene, which is recently recognized to be highly upregulated in human normal ovarian surface epithelium, where it functions as a tumor suppressor [11]

Summary

Introduction

Ovarian cancer is one of the most frequently occurring gynecological cancers, and brings high mortality and morbidity to women the world over [1]. A very diverse group of long non-coding RNAs (lncRNAs) have emerged critical regulators of gene expression and pathway activation in human cancers, including ovarian cancer [6]. We predicted through the LncMAP database that NFkB1 was a putative transcriptional factor regulated by LINC00494, and that FBXO32 was the downstream target gene of NFkB1. FBXO32 (F-box protein 32) is a novel TGF-beta/SMAD4 target gene, which is recently recognized to be highly upregulated in human normal ovarian surface epithelium, where it functions as a tumor suppressor [11]. Long non-coding RNAs (lncRNAs) are recognized as critical governors of gene expression during carcinogenesis, but their effects on the occurrence and development of ovarian cancer require further investigation. We characterized LINC00494 as a novel oncogenic lncRNA in ovarian cancer

Methods

Results

Discussion

Conclusion