The long-noncoding RNA SOCS2-AS1 suppresses endometrial cancer progression by regulating AURKA degradation

Fangfang Jian,Chang Liu,Jingjing Zhang,Yujing Tang,Gedan Liu,Weiwei Feng,Xiaoxia Che

doi:10.1038/s41419-021-03595-x

Fangfang Jian, Chang Liu + Show 5 more

Open Access

https://doi.org/10.1038/s41419-021-03595-x

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Abstract

Aberrant long-noncoding RNA (lncRNA) expression has been shown to be involved in the pathogenesis of endometrial cancer (EC). Herein, we report a novel tumor suppressor lncRNA SOCS2-AS1 in EC. Quantitative real-time PCR was performed to detect RNA expression. In situ hybridization and nuclear/cytoplasmic fractionation assays were used to detect the subcellular location. We found that SOCS2-AS1 was downregulated in EC tissues. Its reduced expression was correlated with advanced clinical stage and poor prognosis. Forced expression of SOCS2-AS1 suppressed EC cell proliferation and induced cell-cycle arrest and apoptosis. SOCS2-AS1-binding proteins were detected using RNA pull-down assay and mass spectrometry. Mechanistically, SOCS2-AS1 bound to Aurora kinase A (AURKA) and increased its degradation through the ubiquitin-proteasome pathway. In conclusion, SOCS2-AS1 may thus serve as a prognostic predictor and a biomarker for AURKA-inhibitor treatment in EC patients.

Highlights

Endometrial cancer (EC) is the most frequently occurring gynecologic cancer in developed countries—with over 319,000 cases diagnosed worldwide, and in excess of 76,000 deaths annually[1]
We demonstrated that SOCS2-AS1 inhibited EC cell proliferation and tumorigenicity in vivo and in vitro, and that low expression levels of SOCS2-AS1 predicted a poor prognosis in EC patients
To identify the functional long-noncoding RNA (lncRNA) involved in EC progression, we executed RNA-seq to profile lncRNA expression in a cohort of normal endometrial tissues (n = 5) and Ec tissues (n = 21)

Summary

Introduction

Endometrial cancer (EC) is the most frequently occurring gynecologic cancer in developed countries—with over 319,000 cases diagnosed worldwide, and in excess of 76,000 deaths annually[1]. Most women diagnosed with EC have early-stage disease and show favorable outcomes, which is true for the well-differentiated, endometrioid histologic subtype[2]. There is a subset of low-grade, early-stage, well-differentiated endometrioid tumors in which unexpected recurrences and poor outcomes do occur[3]. Clinical outcomes worsen considerably for women with recurrent or advanced disease, and for women diagnosed with a clinically aggressive histologic subtype such as the serous histotype[4]. Mounting evidence shows that many lncRNAs are aberrantly expressed in a broad spectrum of cancers, and that they play key roles in promoting and maintaining cancer characteristics[7,8]. Only a few lncRNAs have been shown to be involved in EC— including MEG39, HOTAIR10, MEAT111, MALAT112, BANCR13, H1914, and LINC0067215

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