Xiang Cheng, Cui Shi-Peng, Ke You
Department of General Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
J Huazhong Univ Sci Technolog Med Sci. 2016 Apr;36(2):186-192. doi: 10.1007/s11596-016-1564-0. Epub 2016 Apr 13.
MicroRNAs (miRNAs) modulate the expression of tumorigenesis-related genes and play important roles in the development of various types of cancers. It has been reported that miR-144 is dysregulated and involved in multiple malignant tumors, but its role in renal cell carcinoma (RCC) remains elusive. In this study, we demonstrated miR-144 was significantly downregulated in human RCC. The decreased miR-144 correlated with tumor size and TNM stage. Moreover, overexpression of miR-144 in vitro suppressed RCC cell proliferation and G2 transition, which were reversed by inhibition of miR-144. Bioinformatic analysis predicted that mTOR was a potential target of miR-144, which was further confirmed by dual luciferase reporter assay. Additionally, the examination of clinical RCC specimens revealed that miR-144 was inversely related to mTOR. Furthermore, knocking down mTOR with siRNA had the same biological effects as those of miR-144 overexpression in RCC cells, including cell proliferation inhibition and S/G2 cell cycle arrest. In conclusion, our results indicate that miR-144 affects RCC progression by inhibiting mTOR expression, and targeting miR-144 may act as a novel strategy for RCC treatment.
微小RNA(miRNA)可调节肿瘤发生相关基因的表达,并在各类癌症的发展过程中发挥重要作用。据报道,miR-144表达失调并参与多种恶性肿瘤的发生,但它在肾细胞癌(RCC)中的作用仍不清楚。在本研究中,我们发现miR-144在人肾细胞癌中显著下调。miR-144表达降低与肿瘤大小和TNM分期相关。此外,体外过表达miR-144可抑制肾细胞癌细胞增殖和G2期转化,而抑制miR-144可逆转上述作用。生物信息学分析预测mTOR是miR-144的潜在靶点,双荧光素酶报告基因检测进一步证实了这一点。此外,对临床肾细胞癌标本的检测显示,miR-144与mTOR呈负相关。此外,用小干扰RNA(siRNA)敲低mTOR在肾细胞癌细胞中具有与miR-144过表达相同的生物学效应,包括抑制细胞增殖和使细胞周期停滞在S/G2期。总之,我们的结果表明,miR-144通过抑制mTOR表达影响肾细胞癌进展,靶向miR-144可能成为肾细胞癌治疗的新策略。