Long non-coding RNA SOX2OT promotes the stemness phenotype of bladder cancer cells by modulating SOX2

Yonghao Zhan,Zhicong Chen,Shiming He,Yanqing Gong,Anbang He,Yifan Li,Lianghao Zhang,Xuepei Zhang,Dong Fang,Xuesong Li,Liqun Zhou

doi:10.1186/s12943-020-1143-7

Abstract

BackgroundAccumulating evidence indicates that long non-coding RNAs (lncRNAs) are potential biomarkers and key regulators of tumour development and progression. SOX2 overlapping transcript (SOX2OT) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancer and cancer stem cells. However, the clinical significance and molecular mechanism of SOX2OT in bladder cancer are still unknown.MethodsThe expression level of SOX2OT was determined by RT-qPCR in a total of 106 patients with urothelial bladder cancer and in different bladder cancer cell (BCC) lines. Bladder cancer stem cells (BCSCs) were isolated from BCCs using flow cytometry based on the stem cell markers CD44 and ALDH1. Loss-of-function experiments were performed to investigate the biological roles of SOX2OT in the stemness phenotype of BCSCs. Comprehensive transcriptional analysis, RNA FISH, dual-luciferase reporter assays and western blots were performed to explore the molecular mechanisms underlying the functions of SOX2OT.ResultsSOX2OT was highly expressed in bladder cancer, and increased SOX2OT expression was positively correlated with a high histological grade, advanced TNM stage and poor prognosis. Further experiments demonstrated that knockdown of SOX2OT inhibited the stemness phenotype of BCSCs. Moreover, inhibition of SOX2OT delayed xenograft tumour growth and decreased metastases in vivo. Mechanistically, we found that SOX2OT was mainly distributed in the cytoplasm and positively regulated SOX2 expression by sponging miR-200c. Furthermore, SOX2 overexpression reversed the SOX2OT silencing-induced inhibition of the BCSC stemness phenotype.ConclusionThis study is the first to demonstrate that SOX2OT plays an important regulatory role in BCSCs and that SOX2OT may serve as a potential diagnostic biomarker and therapeutic target in bladder cancer.

Highlights

Urothelial carcinoma of the bladder (UCB) is the sixth most common malignancy in men and the most common genitourinary malignancy worldwide; its incidence and mortality have significantly increased over the past decade [1,2,3,4]
We showed that SOX2 overlapping transcript (SOX2OT) expression was significantly upregulated in bladder cancer tissues compared with in the corresponding normal tissues, and its expression was significantly correlated with histological grade, TNM stage and prognosis
Our results suggest that SOX2OT is a powerful tumour biomarker, which highlights its potential clinical utility as a promising therapeutic and diagnostic target of bladder cancer

Summary

Introduction

Urothelial carcinoma of the bladder (UCB) is the sixth most common malignancy in men and the most common genitourinary malignancy worldwide; its incidence and mortality have significantly increased over the past decade [1,2,3,4]. Accumulating evidence has indicated that SOX2OT is a powerful biomarker involved in the development of multiple cancers and cancer stem cells (CSCs) [27, 28]. Recent studies have provided evidence that SOX2OT plays a positive role in the transcriptional regulation of the SOX2 gene, and the dysregulation of SOX2OT expression has been highlighted in multiple cancers and CSCs [31,32,33]. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are potential biomarkers and key regulators of tumour development and progression. SOX2 overlapping transcript (SOX2OT) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancer and cancer stem cells. The clinical significance and molecular mechanism of SOX2OT in bladder cancer are still unknown

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Results

Discussion

Conclusion