miR-184-5p inhibits cell proliferation, 1 invasion and predicts prognosis of pan cancer by targeting NUS1 dehydrodolichyl diphosphate synthase subunit: Results from large-scale comprehensive identification and validation
miR-184-5p inhibits cell proliferation, 1 invasion and predicts prognosis of pan cancer by targeting NUS1 dehydrodolichyl diphosphate synthase subunit: Results from large-scale comprehensive identification and validation
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miR-184-5p通过靶向NUS1脱氢多羟基二磷酸合酶亚基抑制细胞增殖、1侵袭并预测泛癌预后：大规模综合鉴定和验证结果
作者：
Wangrui Liu;Chunguang Ma;Hong Xu;Lijun Wang;Wenhao Xu;Hailiang Zhang;ZhisuWang;Jun Li;Shuai Zhao;TaoWang
肾透明细胞癌(CcRCC)已成为世界范围内发病率和复发率较高的泌尿生殖系统常见恶性肿瘤。近年来，miRNAs被发现影响肾细胞癌的发生、发展、分子功能和预后。在本研究中，从三个独立的ccRCC队列中鉴定了microRNA-184-5p(miR-184-5p)，并被确定为一个显著不同的预后生物标志物。与HK-2细胞相比，A-498和786-O肾癌细胞中miR-184-5p相对表达。将miR-184-5p模拟物或抑制剂导入肾癌细胞后，检测miR-184-5p对肿瘤细胞增殖、周期、凋亡和侵袭的生物学能力。此外，我们还通过荧光素酶报告和补救实验证实了miR-184-5p与NUS1脱氢二磷酸合酶亚单位(NUS1)之间的直接关系。这些结果表明，miR-184-5p在人肾癌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调控A-498和786-O细胞的增殖、侵袭和凋亡。这些发现可能为慢性肾细胞癌的治疗策略和药物开发提供新的理论靶点。
Clear cell renal cell carcinoma (ccRCC) has become a commonly 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.