Shen Xiaogang, Zuo Xiaofei, Zhang Wenjin, Bai Yifeng, Qin Xianpeng, Hou Nengyi
Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610041, P.R. China.
Department of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan 610083, P.R. China.
Oncol Lett. 2018 Feb;15(2):1673-1679. doi: 10.3892/ol.2017.7524. Epub 2017 Dec 5.
MicroRNA (miR)-370 functions as a tumor suppressor or promoter in several cancers. However, the expression and biological role of miR-370 in colon cancer remains undefined. In the present study, miR-370 expression in both normal and malignant colon tissues was quantified by quantitative polymerase chain reaction. An cell viability and apoptosis assay and an xenograft tumor model were employed to investigate the role of miR-370 on colon cancer growth. Furthermore, the potential direct target of miR-370 was identified using a luciferase assay. Our results demonstrate that down-regulation of miR-370 expression occurs in malignant tissues and miR-370 expression is inversely correlated with tumor grade. Moreover, we determined that miR-370 functions as a tumor suppressor in colon cancer by inhibiting cell proliferation and promoting cell apoptosis. In addition, overexpression of miR-370 impairs xenograft tumor growth in nude mice. Mechanistically, mouse double minute 4 (MDM4) was demonstrated to be a potential direct target of miR-370, inducing apoptosis in colon cancer. Collectively, these findings suggest that upregulation of miR-370 may impair colon tumor growth by directly targeting MDM4. These findings provide a new direction for the diagnosis and treatment of colon cancer.
微小RNA（miR）-370在多种癌症中发挥着肿瘤抑制因子或促进因子的作用。然而，miR-370在结肠癌中的表达及生物学作用仍不明确。在本研究中，通过定量聚合酶链反应对正常和恶性结肠组织中miR-370的表达进行了定量分析。采用细胞活力和凋亡检测以及异种移植肿瘤模型来研究miR-370对结肠癌生长的作用。此外，利用荧光素酶检测确定了miR-370的潜在直接靶点。我们的结果表明，恶性组织中miR-370表达下调，且miR-370表达与肿瘤分级呈负相关。此外，我们确定miR-370在结肠癌中通过抑制细胞增殖和促进细胞凋亡发挥肿瘤抑制作用。另外，miR-370的过表达会损害裸鼠体内异种移植肿瘤的生长。从机制上讲，小鼠双微体4（MDM4）被证明是miR-370的潜在直接靶点，可诱导结肠癌细胞凋亡。总的来说，这些发现表明miR-370的上调可能通过直接靶向MDM4来抑制结肠肿瘤生长。这些发现为结肠癌的诊断和治疗提供了新的方向。
