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miR-184-5p通过靶向NUS1(去氢二萜醇二磷酸合酶亚基)抑制透明细胞肾细胞癌的细胞增殖、侵袭并预测其预后:大规模综合鉴定与验证结果

miR-184-5p inhibits cell proliferation, invasion and predicts prognosis of clear cell renal cell carcinoma by targeting NUS1 dehydrodolichyl diphosphate synthase subunit: Results from large-scale comprehensive identification and validation.

作者信息

Liu Wangrui, Ma Chunguang, Xu Hong, Wang Lijun, Xu Wenhao, Zhang Hailiang, Wang Zhisu, Li Jun, Zhang Ji, Liu Xigao, Zhao Shuai, Wang Tao

机构信息

Department of Interventional Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, China.

出版信息

J Cancer. 2022 Feb 21;13(5):1398-1409. doi: 10.7150/jca.58053. eCollection 2022.

Abstract

Clear cell renal cell carcinoma (ccRCC) has become a common malignant cancer with increasing incidence rate and high recurrence risk in genitourinary oncology around the world. Recently, miRNAs were identified to affect pathogenesis, development, molecular functions, and prognosis of ccRCC. In this study, microRNA-184-5p (miR-184-5p) was identified from three independent ccRCC cohorts and was determined as a significantly distinct prognostic biomarker. Relative miR-184-5p expression was found in A-498 and 786-O ccRCC cells compared with HK-2 cells. After ccRCC cells were transfected with miR-184-5p mimics or inhibitor, biological abilities of miR-184-5p in tumor cell proliferation, cycle, apoptosis and invasion were determined. Additionally, we confirmed the direct relationship between miR-184-5p and NUS1 dehydrodolichyl diphosphate synthase subunit (NUS1) by using the Luciferase reporter and rescue assays. These results indicated that the expression level of miR-184-5p in human ccRCC cells and tissues was reduced, and the up-regulation of miR-184-5p regulated A-498 and 786-O cell proliferation, invasion and apoptosis by directly targeting NUS1. These findings may provide new theoretical targets for treatment strategies and drug development of ccRCC.

摘要

透明细胞肾细胞癌(ccRCC)已成为一种常见的恶性肿瘤,在全球泌尿生殖系统肿瘤中发病率不断上升且复发风险高。最近,研究发现微小RNA(miRNA)会影响ccRCC的发病机制、发展、分子功能和预后。在本研究中,从三个独立的ccRCC队列中鉴定出了微小RNA-184-5p(miR-184-5p),并确定其为一种显著不同的预后生物标志物。与HK-2细胞相比,在A-498和786-O ccRCC细胞中发现了相对的miR-184-5p表达。用miR-184-5p模拟物或抑制剂转染ccRCC细胞后,测定了miR-184-5p在肿瘤细胞增殖、周期、凋亡和侵袭方面的生物学能力。此外,我们通过荧光素酶报告基因和拯救实验证实了miR-184-5p与NUS1脱氢二磷酸多萜醇合酶亚基(NUS1)之间的直接关系。这些结果表明,miR-184-5p在人ccRCC细胞和组织中的表达水平降低,miR-184-5p的上调通过直接靶向NUS1来调节A-498和786-O细胞的增殖、侵袭和凋亡。这些发现可能为ccRCC的治疗策略和药物开发提供新的理论靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c666/8965129/d97ce631d83c/jcav13p1398g001.jpg

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