MiR-378 is an independent prognostic factor and inhibits cell growth and invasion in colorectal cancer

被引:100
作者
Zhang, Guang-jun [1 ,2 ]
Zhou, He [1 ,2 ]
Xiao, Hua-xu [3 ]
Li, Yu [4 ]
Zhou, Tong [1 ,2 ]
机构
[1] North Sichuan Med Coll, Affiliated Hosp, Dept Gen Surg 1, Nanchong, Sichuan, Peoples R China
[2] North Sichuan Med Coll, Inst Hepatobiliary Pancreat & Intestinal Dis, Nanchong, Sichuan, Peoples R China
[3] North Sichuan Med Coll, Dept Pathol, Nanchong, Sichuan, Peoples R China
[4] North Sichuan Med Coll, Dept Microbiol & Parasitol, Nanchong, Sichuan, Peoples R China
关键词
Colorectal cancer; miR-378; Vimentin; Invasion; Prognosis; MICRORNA EXPRESSION PROFILES; VIMENTIN EXPRESSION; BREAST-CANCER; POOR SURVIVAL; TUMOR-GROWTH; METASTASIS; MIGRATION; METHYLATION; BIOGENESIS; SIGNATURE;
D O I
10.1186/1471-2407-14-109
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: MicroRNAs(miRNAs) are small non-coding RNAs that participate in a variety of biologic processes, and dysregulation of miRNA is always associated with cancer development and progression. Aberrant expression of miR-378 has been found in some types of cancer. However, effects and potential mechanisms of miR-378 in colorectal cancer (CRC) have not been explored. Methods: Quantitative RT-PCR was performed to evaluate miR-378 levels in CRC cell lines and 84 pairs of CRC cancer and normal adjacent mucosa. Kaplan-Meier and Cox proportional regression analyses were utilized to determine the association of miR-378 expression with survival of patients. MTT and invasion assays were used to determine the role of miR-378 in regulation of CRC cancer cell growth and invasion, respectively. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. Luciferase assay was performed to assess miR-378 binding to vimentin gene. Results: In this study, we confirmed that miR-378 significantly down-regulated in CRC cancer tissues and cell lines. Moreover, patients with low miR-378 expression had significantly poorer overall survival, and miR-378 expression was an independent prognostic factor in CRC. Over-expression of miR-378 inhibited SW620 cell growth and invasion, and resulted in down-regulation of vimentin expression. However, miR-378 knock-down promoted these processes and enhanced the expression of vimentin. In addition, we further identified vimentin as the functional downstream target of miR-378 by directly targeting the 3'-UTR of vimentin. Conclusions: In conclusion, miR-378 may function as a tumor suppressor and plays an important role in inhibiting tumor growth and invasion. Our present results implicate the potential effects of miR-378 on prognosis and treatment of CRC cancer.
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页数:9
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共 30 条
[1]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[2]   Invasion and metastasis in colorectal cancer:: Epithelial-mesenchymal transition, mesenchymal-epithelial transition, stem cells and β-catenin [J].
Brabletz, T ;
Hlubek, F ;
Spaderna, S ;
Schmalhofer, O ;
Hiendlmeyer, E ;
Jung, A ;
Kirchner, T .
CELLS TISSUES ORGANS, 2005, 179 (1-2) :56-65
[3]   Comparison of Microarray Platforms for Measuring Differential MicroRNA Expression in Paired Normal/Cancer Colon Tissues [J].
Callari, Maurizio ;
Dugo, Matteo ;
Musella, Valeria ;
Marchesi, Edoardo ;
Chiorino, Giovanna ;
Grand, Maurizia Mello ;
Pierotti, Marco Alessandro ;
Daidone, Maria Grazia ;
Canevari, Silvana ;
De Cecco, Loris .
PLOS ONE, 2012, 7 (09)
[4]   International Trends in Colorectal Cancer Incidence Rates [J].
Center, Melissa M. ;
Jemal, Ahmedin ;
Ward, Elizabeth .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2009, 18 (06) :1688-1694
[5]   MicroRNA-378 is associated with non-small cell lung cancer brain metastasis by promoting cell migration, invasion and tumor angiogenesis [J].
Chen, Lan-tao ;
Xu, Shi-dong ;
Xu, Hai ;
Zhang, Jin-feng ;
Ning, Jin-feng ;
Wang, Sheng-fa .
MEDICAL ONCOLOGY, 2012, 29 (03) :1673-1680
[6]   miRNAs, cancer, and stem cell division [J].
Croce, CM ;
Calin, GA .
CELL, 2005, 122 (01) :6-7
[7]   MicroRNA-195 and microRNA-378 mediate tumor growth suppression by epigenetical regulation in gastric cancer [J].
Deng, Hongxia ;
Guo, Yanan ;
Song, Haojun ;
Xiao, Bingxiu ;
Sun, Weiliang ;
Liu, Zhong ;
Yu, Xiuchong ;
Xia, Tian ;
Cui, Long ;
Guo, Junming .
GENE, 2013, 518 (02) :351-359
[8]   miR-378☆ Mediates Metabolic Shift in Breast Cancer Cells via the PGC-1β/ERRγ Transcriptional Pathway [J].
Eichner, Lillian J. ;
Perry, Marie-Claude ;
Dufour, Catherine R. ;
Bertos, Nicholas ;
Park, Morag ;
St-Pierre, Julie ;
Giguere, Vincent .
CELL METABOLISM, 2010, 12 (04) :352-361
[9]   Identification and functional screening of microRNAs highly deregulated in colorectal cancer [J].
Faltejskova, Petra ;
Svoboda, Marek ;
Srutova, Klara ;
Mlcochova, Jitka ;
Besse, Andrej ;
Nekvindova, Jana ;
Radova, Lenka ;
Fabian, Pavel ;
Slaba, Katerina ;
Kiss, Igor ;
Vyzula, Rostislav ;
Slaby, Ondrej .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2012, 16 (11) :2655-2666
[10]   microRNAs: Master Regulators as Potential Therapeutics in Cancer [J].
Garofalo, Michela ;
Croce, Carlo M. .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 51, 2011, 2011, 51 :25-43