Tong Zhigang, Meng Xianfeng, Wang Jinsong, Wang Lixin
Department of Urinary Surgery, The Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Department of Medical Insurance, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin 130021, P.R. China.
Exp Ther Med. 2017 Nov;14(5):5200-5206. doi: 10.3892/etm.2017.5169. Epub 2017 Sep 21.
MicroRNA (miR)-338-3p has been reported to be involved in tumor progression and development in various types of cancer. However, the biological function of miR-338-3p and its related molecular pathways involved in the progression of renal cell carcinoma (RCC) are unknown. The present study aimed to investigate the biological role and underlying mechanism of miR-338-3p in RCC cells. It was demonstrated that miR-338-3p expression level was significantly downregulated (P<0.05) in RCC tissues and cell lines. Clinical association analysis indicated that low expression of miR-338-3p was significantly associated with advanced TNM stage and lymph node metastasis (P<0.05). Function assays revealed that restoration of miR-338-3p in RCC cells significantly inhibited cell proliferation, colony formation, migration and invasion (P<0.05). Notably, sex-determining region Y-box 4 (SOX4) was identified as a direct target of miR-338-3p in RCC cells through a luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blot analysis. Furthermore, SOX4 overexpression partially rescued miR-338-3p-mediated inhibition of cell proliferation, colony formation, migration and invasion in RCC cells. These results suggested that miR-338-3p functioned as a tumor suppressor in RCC cells by modulating SOX4, suggesting that miR-338-3p may have a potential use in the treatment of RCC.
据报道，微小RNA（miR）-338-3p参与多种类型癌症的肿瘤进展和发展。然而，miR-338-3p的生物学功能及其在肾细胞癌（RCC）进展中涉及的相关分子途径尚不清楚。本研究旨在探讨miR-338-3p在RCC细胞中的生物学作用及潜在机制。结果表明，miR-338-3p在RCC组织和细胞系中的表达水平显著下调（P<0.05）。临床关联分析表明，miR-338-3p低表达与晚期TNM分期和淋巴结转移显著相关（P<0.05）。功能分析显示，RCC细胞中miR-338-3p的恢复显著抑制细胞增殖、集落形成、迁移和侵袭（P<0.05）。值得注意的是，通过荧光素酶报告基因检测、逆转录-定量聚合酶链反应和蛋白质印迹分析，确定性别决定区Y盒4（SOX4）是RCC细胞中miR-338-3p的直接靶点。此外，SOX4过表达部分挽救了miR-338-3p介导的RCC细胞增殖、集落形成、迁移和侵袭抑制。这些结果表明，miR-338-3p通过调节SOX4在RCC细胞中发挥肿瘤抑制作用，提示miR-338-3p可能在RCC治疗中具有潜在应用价值。
