Li Mingzi, Yin Bingde, Chen Mulin, Peng Jingtao, Mu Xinyu, Deng Zhen, Xiao Jiantao, Li Weiguo, Fan Jie
Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Department of Urology, Minhang Hospital, Fudan University, Shanghai, China.
Front Oncol. 2021 Feb 19;10:617105. doi: 10.3389/fonc.2020.617105. eCollection 2020.
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 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.
透明细胞肾细胞癌（ccRCC）约占肾细胞癌的75%，是最常见且致命的泌尿系统癌症之一，患者生活质量差，给医疗保健系统带来巨大经济负担。我们迫切需要找到用于ccRCC临床干预的新的预后和治疗靶点。在本研究中，我们发现长链非编码RNA（lncRNA）ASB16-AS1在ccRCC组织中的表达与非病变组织相比下调，并且还与肿瘤晚期和更大的肿瘤相关。通过构建细胞和小鼠模型，发现下调的lncRNA ASB16-AS1增强了细胞增殖、迁移、侵袭，并促进了肿瘤生长和转移。此外，通过进行生物信息学分析、生物素化RNA下拉实验、AGO2-RIP和荧光素酶报告基因检测，我们的研究结果表明，下调的ASB16-AS1通过抑制miR-185-5p和miR-214-3p降低了La相关蛋白1（LARP1）的表达。此外，还发现LARP1的过表达逆转了下调的ASB16-AS1对ccRCC细胞进展的促进作用。我们的结果揭示了下调的ASB16-AS1通过miR-185-5p-miR-214-3p-LARP1途径促进ccRCC进展。我们认为该途径可用于监测预后，并为ccRCC临床管理提供治疗靶点。
