MicroRNA‑16‑5p/BIMP1/NF‑κB axis regulates autophagy to exert a tumor‑suppressive effect on bladder cancer

He,Jiani; Qiu,Zhongkai; Zhang,Hao; Gao,Zhipeng; Jiang,Yuanjun; Li,Zhenhua; Kong,Chuize; Man,Xiaojun

doi:10.3892/mmr.2021.12215

MicroRNA‑16‑5p/BIMP1/NF‑κB axis regulates autophagy to exert a tumor‑suppressive effect on bladder cancer

Authors:
- Jiani He
- Zhongkai Qiu
- Hao Zhang
- Zhipeng Gao
- Yuanjun Jiang
- Zhenhua Li
- Chuize Kong
- Xiaojun Man
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Affiliations: Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Urology, Benxi Central Hospital, Benxi, Liaoning 117000, P.R. China, Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: June 13, 2021 https://doi.org/10.3892/mmr.2021.12215
Article Number: 576
Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bladder cancer (BC) is the second most common urological disease worldwide. Previous studies have reported that microRNA (miR)‑16‑5p is associated with the development of BC, but whether miR‑16‑5p regulates BC cell autophagy remains unknown. Thus, the aim of the present study was to investigate this issue. miR‑16‑5p expression in BC cells was assessed by reverse transcription‑quantitative PCR. Cell viability and apoptosis were detected via Cell Counting Kit‑8 and flow cytometry assays, respectively. For cell autophagy detection, autophagic flux was detected using a mCherry‑green fluorescent protein‑microtubule‑associated proteins 1A/1B light chain 3B (LC3) puncta formation assay, followed by determination of autophagy‑related protein markers. The targeting relationship between miR‑16‑5p and caspase recruitment domain family member 10 (BIMP1) was confirmed using a dual‑luciferase reporter assay, followed by detection of the BIMP1/NF‑κB signaling pathway. The results showed that miR‑16‑5p overexpression inhibited cell viability, whereas miR‑16‑5p knockdown promoted cell viability in BC. Furthermore, miR‑16‑5p overexpression induced autophagy, which was accompanied by increased autophagic flux and expression of the autophagy‑related proteins LC3‑II and beclin 1, as well as decreased p62 expression, whereas miR‑16‑5p silencing led to an inhibition of autophagy in BC cells. Moreover, autophagy inhibitor 3‑methyladenine treatment inhibited cell autophagy and apoptosis in miR‑16‑5p‑overexpressing cells. Mechanistic studies demonstrated that miR‑16‑5p could inhibit the BIMP1/NF‑κB signaling pathway and this inhibition was achieved by directly targeting BIMP1. Furthermore, it was found that blockade of the BIMP1/NF‑κB signaling pathway inversed the inhibitory effects of miR‑16‑5p knockdown on autophagy in BC cells. In vivo experiments further verified the tumor‑suppressive effect on BC of the miR‑16‑5p/BIMP1/NF‑κB axis. Therefore, the results of the present study indicated that miR‑16‑5p promotes autophagy of BC cells via the BIMP1/NF‑κB signaling pathway, and an improved understanding of miR‑16‑5p function may provide therapeutic targets for clinical intervention in this disease.

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