Downregulation of the lncRNA ASB16-AS1 Decreases LARP1 Expression and Promotes Clear Cell Renal Cell Carcinoma Progression via miR-185-5p/miR-214-3p

Mingzi Li; Bingde Yin; Mulin Chen; Jingtao Peng; Xinyu Mu; Zhen Deng; Jiantao Xiao; Weiguo Li; Jie Fan

doi:10.3389/fonc.2020.617105

Downregulation of the lncRNA ASB16-AS1 Decreases LARP1 Expression and Promotes Clear Cell Renal Cell Carcinoma Progression via miR-185-5p/miR-214-3p

Front Oncol. 2021 Feb 19:10:617105. doi: 10.3389/fonc.2020.617105. eCollection 2020.

Authors

Mingzi Li¹, Bingde Yin², Mulin Chen¹, Jingtao Peng³, Xinyu Mu¹, Zhen Deng¹, Jiantao Xiao⁴, Weiguo Li¹, Jie Fan¹

Affiliations

¹ Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
² Department of Urology, Minhang Hospital, Fudan University, Shanghai, China.
³ Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Abstract

Clear cell renal cell carcinoma (ccRCC) comprises approximately 75% of renal cell carcinomas, which is one of the most common and lethal urologic cancers, with poor quality of life for patients and is a huge economic burden to health care systems. It is imperative we find novel prognostic and therapeutic targets for ccRCC clinical intervention. In this study, we found that the expression of the long noncoding RNA (lncRNA) ASB16-AS1 was downregulated in ccRCC tissues compared with non-diseased tissues and was also associated with advanced tumor stage and larger tumors. By constructing cell and mouse models, it was found that downregulated lncRNA ASB16-AS1 enhanced cell proliferation, migration, invasion, and promoted tumor growth and metastasis. Furthermore, by performing bioinformatics analysis, biotinylated RNA pull-downs, AGO2-RIP, and luciferase reporter assays, our findings showed that downregulated ASB16-AS1 decreased La-related protein 1 (LARP1) expression by inhibiting miR-185-5p and miR-214-3p. Furthermore, it was found that overexpression of LARP1 reversed the promotive effects of downregulated ASB16-AS1 on ccRCC cellular progression. Our results revealed that downregulated ASB16-AS1 promotes ccRCC progression via a miR-185-5p-miR-214-3p-LARP1 pathway. We suggest that this pathway could be used to monitor prognosis and presents therapeutic targets for ccRCC clinical management.

Keywords: LARP1; clear cell renal cell carcinoma; lncRNA ASB16-AS1; long non-coding RNA; miR-185-5p; miR-214-3p.