FTO promotes tumour proliferation in bladder cancer via the FTO/miR-576/CDK6 axis in an m6A-dependent manner

Guanwen Zhou,Lijian Gao,Keqiang Yan,Jikai Liu,Yidong Fan,Xianzhou Jiang

doi:10.1038/s41420-021-00724-5

Abstract

The aberrant expression of fat mass and obesity-associated protein (FTO) has been confirmed to be associated with a variety of cancers and participates in the regulation of multiple biological behaviours. FTO plays an oncogenic role in bladder cancer, but few studies have focused on how FTO promotes bladder cancer progression by regulating miRNA synthesis. Here, we confirmed that FTO expression was significantly increased in bladder cancer and was associated with a poor prognosis. FTO overexpression promoted bladder cancer cell proliferation, whereas FTO knockdown inhibited bladder cancer cell proliferation. We also demonstrated that FTO promoted bladder cancer cell proliferation via the FTO/miR-576/CDK6 pathways. Taken together, our work revealed that FTO plays a critical role in bladder cancer and could be a potential diagnostic or prognostic biomarker for this disease.

Highlights

Bladder cancer is a complex disease associated with high morbidity and mortality rates if not optimally treated [1]
A negative correlation was observed between php), we found that miR-19a, miR-17, miR-590, miR-93, miR-576 miR-576 and Cyclin-dependent kinase 6 (CDK6) expressions (r = −0.75, P < 0.001) (Fig. 7B), and miR-192 were negatively correlated with fat mass and obesity-associated (FTO) in bladder whereas a positive correlation was observed between FTO and cancer (Supplementary Fig. 2)
M6A was formation by regulating miRNA synthesis, our study demonstrated immunoprecipitated from FTO-overexpressing T24 cells and that FTO could promote bladder cancer proliferation via the FTO/

Summary

INTRODUCTION

Bladder cancer is a complex disease associated with high morbidity and mortality rates if not optimally treated [1]. Some studies have shown that FTO affects tumour progression via regulating microRNA (miRNA) expression [11, 12]. MicroRNAs(miRNAs) are responsible for the regulation of gene expression at the post-transcriptional modification manner by targeting mRNAs and forming RNA-induced silencing complexes (RISC), thereby regulating cell growth, proliferation, differentiation and apoptosis. The present study demonstrated that FTO exhibited an oncogenic role in bladder cancer via regulating the expression of cyclin-dependent kinases (CDK6), which are closely related to the cell cycle. Patients with bladder cancer exhibiting high FTO levels may have a worse prognosis. This indicates that FTO exhibits an oncogenic role via the FTO/miR-576/CDK6 pathways in bladder cancer and could be a potential diagnostic or prognostic biomarker for bladder cancer

RESULT

DISCUSSION

Findings

MATERIALS AND METHODS