Long Non-coding RNA DLEU1 Promotes Cell Proliferation, Invasion, and Confers Cisplatin Resistance in Bladder Cancer by Regulating the miR-99b/HS3ST3B1 Axis.

Yongzhi Li,Xingwang Zhu,Bing Liu,Benkang Shi,Yili Liu,Fengming Dong

doi:10.3389/fgene.2019.00280

Abstract

Although accumulating evidence has shown the important function of long non-coding RNAs (lncRNAs) in tumor progression and chemotherapy resistance, the role of lncRNA DLEU1 in regulating proliferation, invasion, and chemoresistance of bladder cancer (BCA) cells remains largely unknown. Here, we found that DLEU1 was upregulated in BLCA tissues and BCA patients with high DLEU1 expression exhibited a shorter survival time. Furthermore, mechanistic analysis and functional assays validated that DLEU1 induced cell proliferation, invasion, and cisplatin resistance of BCA cells by de-repressing the expression of HS3ST3B1 through sponging miR-99b. Low miR-99b and high HS3ST3B1 levels were correlated with worse prognosis in patients with BCA. Ectopic expression of HS3ST3B1 or inhibition of miR-99b reversed DLEU1 knockdown-mediated suppression of cell proliferation, invasion, and cisplatin resistance. Thus, our study revealed a novel role for the DLEU1/miR-99b/HS3ST3B1 axis in regulating proliferation, invasion, and cisplatin resistance of BCA cells.

Highlights

Bladder cancer (BCA) is one of the most common urological malignancies, with an estimated 76,960 new cases and 16,390 deaths in the United States in 2016 (Siegel et al, 2016)
In order to investigate the relevance of DLEU1 in BCA development, we first checked its expression using the TCGA BCA dataset through the UALCAN web portal (Chandrashekar et al, 2017)
To test whether DLEU1 exerts oncogenic functions in BCA by modulating the miR-99b/HS3ST3B1 axis, we investigated the effects of miR-99b or HS3ST3B1 on DLEU1-induced cancer cell proliferation, invasion, and cisplatin resistance

Summary

Introduction

Bladder cancer (BCA) is one of the most common urological malignancies, with an estimated 76,960 new cases and 16,390 deaths in the United States in 2016 (Siegel et al, 2016). An increasing number of studies have reported that the dysregulation of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) can regulate the progression and chemoresistance of human tumors (Anastasiadou et al, 2018). The DLEU1/miR-99b/HS3ST3B1 Axis in Bladder Cancer of greater than 200 nucleotides and can act as molecular sponges, scaffolds, and guides to interact with proteins, mRNAs, or miRNAs, thereby regulating the expression of target genes (Anastasiadou et al, 2018; Dong et al, 2018). Growing evidence indicated that the interactions between lncRNAs and miRNAs play crucial roles in modulating tumor progression and chemoresistance (Cao et al, 2017; Chen et al, 2019)

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