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Open Access Highly Accessed Research article

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

Guang-jun Zhang12, He Zhou12, Hua-xu Xiao3, Yu Li4 and Tong Zhou12*

Author Affiliations

1 The First Department of General Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China

2 Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China

3 Department of Pathology, The North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China

4 Department of Microbiology and Parasitology, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China

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BMC Cancer 2014, 14:109  doi:10.1186/1471-2407-14-109

Published: 20 February 2014

Abstract

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.

Keywords:
Colorectal cancer; miR-378; Vimentin; Invasion; Prognosis