Shen Yu, Chen Haiqun, Gao Ling, Zhang Weigang, He Jun, Yang Xiaohua, Qin Lei, Xue Xiaofeng, Guo Zhaoji
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, P.R. China.
Department of General Surgery, Xinhua Hospital Affiliated to Jiaotong University Chongming Branch, Shanghai 200000, P.R. China.
Oncotarget. 2017 Nov 20;8(64):108170-108180. doi: 10.18632/oncotarget.22567. eCollection 2017 Dec 8.
Gastric cancer is one of the major causes of cancer mortality. Several microRNAs play a role in the tumor growth and invasion. However, the underlying molecular mechanism remains poorly understood. We detected the miR-638 expression levels in tumor samples and adjacent noncancerous tissues from 68 patients with gastric cancer as well as in the gastric cancer cell line SGC-7901 and SC-M1. The cell cycle was analyzed by flow cytometry, cell proliferation was observed by CCK-8 assay and cell invasion was detected using Transwell assay. MiR-638 was down-regulated in human GC tissues and its expression level was negatively correlated to TNM stage and lymph metastasis. In the cell lines, aberrant expression of miR-638 was related to the cell proliferation, cell cycle and invasion. We also found that SOX2 had a negative correlation with miR-638 in GC tissues, and miR-638 overexpression could decrease SOX2 expression level by directly binding the 3'-UTR of SOX2. , down-regulating SOX2 by siRNA could counteract the effect of miR-638 inhibitor on GC cells proliferation and invasion. Our results demonstrate that miR-638 may play a pivotal role in the growth and invasion of GC.
胃癌是癌症死亡的主要原因之一。几种微小RNA在肿瘤生长和侵袭中发挥作用。然而,其潜在的分子机制仍知之甚少。我们检测了68例胃癌患者肿瘤样本及癌旁非癌组织以及胃癌细胞系SGC-7901和SC-M1中miR-638的表达水平。通过流式细胞术分析细胞周期,采用CCK-8法观察细胞增殖情况,并使用Transwell法检测细胞侵袭能力。miR-638在人胃癌组织中表达下调,其表达水平与TNM分期及淋巴转移呈负相关。在细胞系中,miR-638的异常表达与细胞增殖、细胞周期及侵袭有关。我们还发现,在胃癌组织中SOX2与miR-638呈负相关,miR-638过表达可通过直接结合SOX2的3'-UTR降低SOX2表达水平。此外,通过siRNA下调SOX2可抵消miR-638抑制剂对胃癌细胞增殖和侵袭的影响。我们的结果表明,miR-638可能在胃癌的生长和侵袭中起关键作用。