Ji Hong, Tian Dong, Zhang Bing, Zhang Yangyang, Yan Dongliang, Wu Shuhua
Department of Pathology, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China.
Department of Urology, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China.
Exp Ther Med. 2017 May;13(5):2286-2292. doi: 10.3892/etm.2017.4263. Epub 2017 Mar 24.
MicroRNA-155 (miR-155) is overexpressed in numerous human cancer types and has an oncogenic role. Previous study has revealed that miR-155 serves an important role in the progression of clear-cell renal cell carcinoma (ccRCC); however, the underlying mechanism was not completely clarified. The present study aimed to investigate the biological role of miR-155 in ccRCC and the underlying molecular mechanisms. The expression of miR-155 in 20 ccRCC and adjacent normal kidney tissues was determined by PCR. After downregulation of miR-155 expression by miR-155 inhibitor, cell growth was assessed by MTT and colony formation assays. Apoptosis and cell cycle distribution were analyzed by flow cytometry. Cell invasion and migration was detected by wound healing and Transwell assays. Furthermore, forkhead box O3a (FOXO3a) mRNA and protein expression were detected by PCR and immunoblotting. The expression of FOXO3a in 20 ccRCC tissues was also examined by immunohistochemistry. The expression of miR-155 was upregulated in ccRCC tissues compared to that in adjacent normal tissues. Inhibition of miR-155 significantly suppressed the proliferation, colony formation, migration and invasion, and induced G1 arrest and apoptosis of ccRCC cells . Moreover, inhibition of miR-155 significantly upregulated FOXO3a expression, and miR-155 expression was inversely correlated with FOXO3a expression in ccRCC tissues. In conclusion, miR-155 may have an important role in the genesis of ccRCC through targeting FOXO3a and may be a potential target for ccRCC therapy.
微小RNA-155(miR-155)在多种人类癌症类型中过表达,并具有致癌作用。先前的研究表明,miR-155在透明细胞肾细胞癌(ccRCC)的进展中起重要作用;然而,其潜在机制尚未完全阐明。本研究旨在探讨miR-155在ccRCC中的生物学作用及其潜在的分子机制。通过PCR测定20例ccRCC组织及相邻正常肾组织中miR-155的表达。用miR-155抑制剂下调miR-155表达后,通过MTT和集落形成试验评估细胞生长。通过流式细胞术分析细胞凋亡和细胞周期分布。通过伤口愈合试验和Transwell试验检测细胞侵袭和迁移。此外,通过PCR和免疫印迹检测叉头框O3a(FOXO3a)mRNA和蛋白表达。还通过免疫组织化学检测20例ccRCC组织中FOXO3a的表达。与相邻正常组织相比,ccRCC组织中miR-155的表达上调。抑制miR-155可显著抑制ccRCC细胞的增殖、集落形成、迁移和侵袭,并诱导G1期阻滞和细胞凋亡。此外,抑制miR-155可显著上调FOXO3a表达,且ccRCC组织中miR-155表达与FOXO3a表达呈负相关。总之,miR-155可能通过靶向FOXO3a在ccRCC的发生中起重要作用,可能是ccRCC治疗的潜在靶点。