miR-20a is an independent prognostic factor in colorectal cancer and is involved in cell metastasis

被引:44
作者
Zhang, Guang-Jun [1 ]
Li, Yu [1 ]
Zhou, He [1 ]
Xiao, Hua-Xu [1 ]
Zhou, Tong [1 ]
机构
[1] North Sichuan Med Coll, Dept Gen Surg 1, Inst Hepatobiliary Pancreas & Intestinal Dis, Affiliated Hosp, Nanchong 637000, Sichuan, Peoples R China
关键词
miR-20a; colorectal cancer; epithelial-mesenchymal transition; metastasis; prognostic factor; EPITHELIAL-MESENCHYMAL TRANSITION; COLON-CARCINOMA CELLS; POOR SURVIVAL; EXPRESSION; SMAD4; PROLIFERATION; PROMOTES; INVASION; GROWTH; GENE;
D O I
10.3892/mmr.2014.2144
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Accumulating evidence indicates that dysregulated microRNAs (miRNAs) are involved in cancer development, progression and metastasis. miR-20a was found to be involved in invasion and epithelial-mesenchymal transition (EMT) programs, with its aberrant expression having been observed in a variety of malignant tumors. However, the molecular mechanisms underlying the role of miR-20a in colorectal cancer (CRC) development remain to be fully elucidated. In the present study, the expression of miR-20a was compared between CRC tissue samples and the normal adjacent mucosa using quantitative polymerase chain reaction. The association of miR-20a expression with clinicopathological characteristics was assessed using appropriate statistical analysis. The migration and invasion of SW480 cells was examined following transfection of the cells with either miR-20a precursor or a negative control miRNA precursor. The effect of miR-20a on the EMT in CRC cells in vitro was also analyzed. The regulatory effect of miR-20a on SMAD family member 4 (SMAD4) was evaluated using a dual-luciferase reporter assay. Relative expression levels of miR-20a were significantly higher in CRC tissue than those in the normal adjacent mucosa, and high expression of miR-20a correlated with lymph node metastases and distant metastases. Kaplan-Meier analysis indicated that patients with increased miR-20a levels exhibited unfavorable overall survival. Furthermore, multivariate analysis showed that miR-20a was an independent prognostic factor. The transfection of SW480 CRC cells with miR-20a promoted migration and invasion in vitro, and the upregulation of miR-20a induced EMT in CRC cells. An inverse correlation between the levels of miR-20a and SMAD4 was observed in patients with CRC. Overexpression of miR-20a in CRC cells decreased SMAD4 expression and decreased SMAD4-driven luciferase reporter activity. The present study revealed that miR-20a was an independent prognostic factor in CRC. Furthermore, miR-20a induced EMT and regulated migration and invasion of SW480 cells, at least in part via suppression of SMAD4 expression. The present study suggests that miR-20a may serve as a novel prognostic marker and therapeutic target for CRC.
引用
收藏
页码:283 / 291
页数:9
相关论文
共 38 条
[31]   Epithelial-mesenchymal transition in cancer metastasis: Mechanisms, markers and strategies to overcome drug resistance in the clinic [J].
Voulgari, Angeliki ;
Pintzas, Alexander .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2009, 1796 (02) :75-90
[32]   Inactivation of SMAD4 tumor suppressor gene during gastric carcinoma progression [J].
Wang, Li-Hui ;
Kim, Seok-Hyung ;
Lee, Jung Hyun ;
Choi, Yoon-La ;
Kim, Young Chul ;
Park, Tae Sung ;
Hong, Yun-Chul ;
Wu, Chun-Fu ;
Shin, Young Kee .
CLINICAL CANCER RESEARCH, 2007, 13 (01) :102-110
[33]   MicroRNA-20a Overexpression Inhibited Proliferation and Metastasis of Pancreatic Carcinoma Cells [J].
Yan, Haijiao ;
Wu, Jiangxue ;
Liu, Wensong ;
Zuo, Yufang ;
Chen, Shupeng ;
Zhang, Shineng ;
Zeng, Musheng ;
Huang, Wenlin .
HUMAN GENE THERAPY, 2010, 21 (12) :1723-1734
[34]   MicroRNA-93 inhibits tumor growth and early relapse of human colorectal cancer by affecting genes involved in the cell cycle [J].
Yang, I-Ping ;
Tsai, Hsiang-Lin ;
Hou, Ming-Feng ;
Chen, Ku-Chung ;
Tsai, Pei-Chien ;
Huang, Szu-Wei ;
Chou, Wen-Wen ;
Wang, Jaw-Yuan ;
Juo, Suh-Hang Hank .
CARCINOGENESIS, 2012, 33 (08) :1522-1530
[35]   Mechanism of the Mesenchymal-Epithelial Transition and Its Relationship with Metastatic Tumor Formation [J].
Yao, Dianbo ;
Dai, Chaoliu ;
Peng, Songlin .
MOLECULAR CANCER RESEARCH, 2011, 9 (12) :1608-1620
[36]   Prognostic values of the miR-17-92 cluster and its paralogs in colon cancer [J].
Yu, Ge ;
Tang, Jian-Qiang ;
Tian, Mao-Lin ;
Li, Hui ;
Wang, Xin ;
Wu, Tao ;
Zhu, Jing ;
Huang, Shan-Jun ;
Wan, Yuan-Lian .
JOURNAL OF SURGICAL ONCOLOGY, 2012, 106 (03) :232-237
[37]   Upregulation of microRNA-155 promotes the migration and invasion of colorectal cancer cells through the regulation of claudin-1 expression [J].
Zhang, Guang-Jun ;
Xiao, Hua-Xu ;
Tian, Hong-Peng ;
Liu, Zuo-Liang ;
Xia, Shu-Sen ;
Zhou, Tong .
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2013, 31 (06) :1375-1380
[38]   Clinical significance of miR-22 expression in patients with colorectal cancer [J].
Zhang, Guangjun ;
Xia, Shusen ;
Tian, Hongpeng ;
Liu, Zuoliang ;
Zhou, Tong .
MEDICAL ONCOLOGY, 2012, 29 (05) :3108-3112