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

Abstract

BackgroundMicroRNAs(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.MethodsQuantitative 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.ResultsIn 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.ConclusionsIn 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.

Decreased expression of miR-874 and its tumor suppressive function in human colorectal cancer

“…Zheng et al (2014) indicated that downregulation of miR-132 in CRC was associated with tumor size, distant metastasis, and TNM stage. Furthermore,, and miR-378a-5p expressions were identified as independent prognostic factors for CRC (Yu et al, 2013;Zhang et al, 2014a). miR-129 sensitized CRC cells to 5-FU both in vitro and in vivo (Karaayvaz et al, 2013), and miR-124 increased the radiosensitivity of CRC cells (Zhang et al 2014b).…”

MiR-378 Promotes the Migration of Liver Cancer Cells by Down-Regulating Fus Expression

“…miRNAs pair with the messages of protein-coding genes to direct post-transcriptional repression [3] and target mRNAs based on sequence complementarity with target 3′-untranslated regions (3′-UTRs), leading to translational repression and/or to mRNA cleavage [4]. miRNAs are involved in cell differentiation [5], apoptosis [6], cell proliferation [7,8], division [9], protein secretion [10], immune regulation [11], viral infection [12], cancer development [13,14], invasion [15,16], tissue morphogenesis and growth [17,18], angiogenesis [19,20] and metastasis [21]. The largest functional group of miRNAs are those miRNAs involved in cancer development, and among these, some have been reported to function as oncogenic miRNAs or tumor suppressors, whereas others exert diverse functions [22].…”

Lack of association between an insertion/deletion polymorphism in IL1A and risk of colorectal cancer

“…By binding to the 3' UTRs of target genes, miRNAs play important roles in tumor pathogenesis. The expression of miR-378 is known to be downregulated in both plasma and tumor tissue in CRC patients (Zanutto et al, 2014;Zhang et al, 2014a). Overexpression of miR-378 can inhibit cell growth and invasion, while its downregulation may promote these processes (Zhang et al, 2014a), suggesting that this miRNA may function as a tumor suppressor in CRC.…”