Circular RNA circGLIS3 promotes bladder cancer proliferation via the miR-1273f/SKP1/Cyclin D1 axis

Shuilian Wu,Xin Wang,Aruo Nan,Wenmin Lu,Jie Yang,Ruirui Zhang,Jialei Yang,Yunfeng Zou,Sixian Chen,Haotian Xu,Xiaofei Li

doi:10.1007/s10565-021-09591-3

Shuilian Wu, Xin Wang + Show 9 more

Open Access

https://doi.org/10.1007/s10565-021-09591-3

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Abstract

Extensive research confirmed that circRNA can play a regulatory role in various stages of tumors by interacting with various molecules. Identifying the differentially expressed circRNA in bladder cancer and exploring its regulatory mechanism on bladder cancer progression are urgent. In this study, we screened out a circRNA-circGLIS3 with a significant upregulation trend in both bladder cancer tissues and cells. Bioinformatics prediction results showed that circGLIS3 may be involved in multiple tumor-related pathways. Function gain and loss experiments verified circGLIS3 can affect the proliferation, migration, and invasion of bladder cancer cells in vitro. Moreover, silencing circGLIS3 inhibited bladder cancer cell growth in vivo. Subsequent research results indicated circGLIS3 regulated the expression of cyclin D1, a cell cycle–related protein, and cell cycle progression. Mechanically, circGLIS3 upregulates the expression of SKP1 by adsorbing miR-1273f and then promotes cyclin D1 expression, ultimately promoting the proliferation of bladder cancer cells. In summary, our study indicates that circGLIS3 plays an oncogene role in the development of bladder cancer and has potential to be a candidate for bladder cancer.Graphical abstract

Highlights

Bladder cancer, a malignant tumor, has the highest incidence in the human urinary system
We found for the first time that, compared with normal bladder epithelial cells, circGLIS3 expression was significantly increased in bladder cancer cells through microarray analysis
CircGLIS3 expression is upregulated in bladder cancer

Summary

Introduction

A malignant tumor, has the highest incidence in the human urinary system. According to the clinicopathologic classification, bladder cancer is primarily divided into two subtypes, including muscular invasive type and non-muscular invasive type. Most patients with non-muscular invasive bladder cancer are treated with surgical resection or combined chemotherapy. Bladder cancer remains difficult to cure (Sun and Trinh 2015; Alfred Witjes et al 2017), with the rapid development of molecular technology, many diagnostic markers and therapeutic targets have been discovered. Discovery of these molecules will greatly promote the diagnosis and treatment of bladder cancer

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