Lnc-STYK1-2 regulates bladder cancer cell proliferation, migration, and invasion by targeting miR-146b-5p expression and AKT/STAT3/NF-kB signaling

Ranran Dai,Qingping Jiang,Yumin Zhang,Ruifeng Lin,Hai Lin,Jinhu Zhang,Xingcheng Gao,You Zhou

doi:10.1186/s12935-021-02114-4

Abstract

BackgroundEpigenetic modulation by noncoding RNAs substantially contributes to human cancer development, but noncoding RNAs involvement in bladder cancer remains poorly understood. This study investigated the role of long noncoding RNA (lncRNA) lnc-STYK1-2 in tumorigenesis in cancerous bladder cells.MethodsDifferential lncRNA and mRNA profiles were characterized by high-throughput RNA sequencing combined with validation via quantitative PCR. Bladder cancer cell proliferation was assessed through MTS, and bladder cancer cell migration and invasion were assessed through a Transwell system. The in vivo tumorigenesis of bladder cancer cells was evaluated using the cancer cell line-based xenograft model. The dual-luciferase reporter assay verified the association of miR-146b-5p with lnc-STYK1-2 and the target gene. Protein abundances and phosphorylation were detected by Western blotting.ResultsAlterations in lncRNA profiles, including decreased lnc-STYK1-2 expression, were detected in bladder cancer tissues compared with adjacent noncancerous tissues. lnc-STYK1-2 silencing effectively promoted proliferation, migration, and invasion in two bladder cancer cell lines, 5637 and T24, and their tumorigenesis in nude mice. lnc-STYK1-2 siRNA promoted miR-146b-5p and reduced ITGA2 expression in bladder cancer cells. Moreover, miR-146b-5p suppressed ITGA2 expression in bladder cancer cells through direct association. Also, lnc-STYK1-2 directly associated with miR-146b-5p. Finally, miR-146b-5p inhibitors abrogated the alterations in bladder cell functions, ITGA2 expression, and phosphorylation of AKT, STAT3, and P65 proteins in 5637 and T24 cells induced by lnc-STYK1-2 silencing.Conclusionlnc-STYK1-2 inhibited bladder cancer cell proliferation, migration, and tumorigenesis by targeting miR-146b-5p to regulate ITGA2 expression and AKT/STAT3/NF-kB signaling.

Highlights

Epigenetic modulation by noncoding RNAs substantially contributes to human cancer development, but noncoding RNAs involvement in bladder cancer remains poorly understood
Altered long noncoding RNA (lncRNA) profiles and decreased lnc‐STYK1‐2 expression in bladder cancer tissues To investigate the potential roles of lncRNAs in bladder cancer pathogenesis, we first characterized the differentially expressed lncRNAs in bladder cancer tissues collected from three bladder cancer patients
We observed that the expression of lnc-STYK1-2 in bladder cancer tissues was greatly downregulated compared with that in adjacent tissues, which were further validated by quantitative RT-PCR in another 16 bladder cancer tissues (Fig. 1D)

Summary

Introduction

Epigenetic modulation by noncoding RNAs substantially contributes to human cancer development, but noncoding RNAs involvement in bladder cancer remains poorly understood. Long noncoding RNAs (lncRNAs) are a huge group of transcripts in a size of more than 200 nt without proteincoding functions. They are prevalently expressed in various tissues and cell types in almost all species [7,8,9]. The expression profiles of lncRNAs were significantly altered with a high correlation with cancer formation, development, metastasis, and 5-year survival rates [12, 13]. Proliferation rates and metastasis of bladder cancer cells could be substantially regulated by the lncRNA SPRY4-IT1 (SPRY4 intronic transcript 1), mediated by its impact on the expression of enhancer of zeste homolog 2 (EZH2) [15]. The pathogenic roles of new lncRNAs in bladder cancer development need further elucidation, considering the many differentially expressed lncRNAs in bladder cancer cells

Methods

Results

Discussion

Conclusion