Downregulation of the lncRNA ASB16-AS1 Decreases LARP1 Expression and Promotes Clear Cell Renal Cell Carcinoma Progression via miR-185-5p/miR-214-3p.
Downregulation of the lncRNA ASB16-AS1 Decreases LARP1 Expression and Promotes Clear Cell Renal Cell Carcinoma Progression via miR-185-5p/miR-214-3p.
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lncRNA ASB16-AS1 的下调可降低 LARP1 表达并通过 miR-185-5p/miR-214-3p 促进透明细胞肾细胞癌进展
DOI：
10.3389/fonc.2020.617105
复制
发表时间：
2020
影响因子：
4.7
通讯作者：
Fan J
中科院分区：
文献类型：
--
作者：
Li M;Yin B;Chen M;Peng J;Mu X;Deng Z;Xiao J;Li W;Fan J
肾透明细胞癌约占肾细胞癌的75%，是最常见和最致命的泌尿系肿瘤之一，患者的生活质量较差，是医疗保健系统的巨大经济负担。寻找新的预后和治疗靶点是肾细胞癌临床干预的当务之急。在本研究中，我们发现长非编码RNA(LncRNA)ASB16-AS1在肾细胞癌组织中的表达与非病变组织相比下调，并与晚期肿瘤分期和较大的肿瘤有关。通过构建细胞和小鼠模型，发现下调的lncRNA ASB16-AS1促进了细胞的增殖、迁移、侵袭，并促进了肿瘤的生长和转移。此外，通过生物信息学分析、生物素化RNA下拉、AGO2-RIP和荧光素酶报告分析，我们的发现表明下调的ASB16-AS1通过抑制miR-185-5p和miR-214-3p而降低La相关蛋白1(LARP1)的表达。此外，研究还发现，LARP1的过表达逆转了下调的ASB16-AS1对肾细胞癌细胞进展的促进作用。我们的结果表明，下调的ASB16-AS1通过miR-185-5p-miR-214-3p-LARP1途径促进肾细胞癌的进展。我们认为该通路可用于监测预后，并为临床治疗提供靶点。
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.
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DOI：
10.1126/science.1199498
发表时间：
2011-06-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hsu PP;Kang SA;Rameseder J;Zhang Y;Ottina KA;Lim D;Peterson TR;Choi Y;Gray NS;Yaffe MB;Marto JA;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
14.9
作者：
Philippe, Lucas;Vasseur, Jean-Jacques;Thoreen, Carson C.
通讯作者：
Thoreen, Carson C.
影响因子：
11.2
作者：
Bhan A;Soleimani M;Mandal SS
通讯作者：
Mandal SS
影响因子：
4
作者：
Liu, Yunfei;Wang, Jiale;Yu, Xiao
通讯作者：
Yu, Xiao
影响因子：
14.9
作者：
Hopkins TG;Mura M;Al-Ashtal HA;Lahr RM;Abd-Latip N;Sweeney K;Lu H;Weir J;El-Bahrawy M;Steel JH;Ghaem-Maghami S;Aboagye EO;Berman AJ;Blagden SP
通讯作者：
Blagden SP