Our results demonstrated that miR-92a induced EMT and regulated cell growth, migration and invasion in the SW480 cells, at least partially, via suppression of PTEN expression. MiR-92a may serve as a novel therapeutic target in colorectal cancer.

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.

Human microRNA-155 (miR-155) has been demonstrated to regulate a variety of cellular functions, including epithelial-to-mesenchymal transition (EMT) by targeting multiple messenger RNAs (mRNAs). However, its role in colorectal cancer (CRC) remains unelucidated. Therefore, the aim of the present study was to investigate the effects of miR-155 on CRC cells. The expression level of miR-155 was quantified by quantitative real-time reverse transcriptase-PCR (qRT-PCR) in primary CRC tissues and normal adjacent mucosa. MTT, migration and invasion assays were used to examine the proliferation, migration and invasion of SW480 cells transfected with miR‑155. The expression of miR-155 was significantly upregulated in the CRC tissues and the high expression of miR-155 correlated with an advanced clinical stage, lymph node and distant metastases. The ectopic expression of miR-155 enhanced the migration and invasive ability of the SW480 cells and altered their morphological appearance; however, cell proliferation was not affected. E-cadherin expression levels decreased, while ZEB1 expression levels increased in the SW480 cells overexpressing miR-155. Furthermore, the overexpression of miR-155 upregulated claudin-1 expression. Thus, our data suggest that miR-155 plays an important role in promoting CRC cell migration and invasion, at least in part through the regulation of claudin-1 expression and controlling metastasis in CRC.

BackgroundGrowing evidence suggests that microRNAs (miRNAs) play an important role in tumor development, progression and metastasis. Aberrant miR-106b expression has been reported in several cancers. However, the role and underlying mechanism of miR-106 in colorectal cancer (CRC) have not been addressed.MethodsQuantitative RT-PCR(qRT-PCR) was performed to evaluate miR-106b levels in CRC cell lines and patient specimens. Cell proliferation was detected using MTT assay, and cell migration and invasion ability were evaluated by wound healing assay and transwell assay. The target gene of miR-106b was determined by qRT-PCR, western blot and luciferase assays.ResultsmiR-106b was significantly up-regulated in metastatic CRC tissues and cell lines, and high miR-106b expression was associated with lymph node metastasis and advanced clinical stage. In addition, miR-106b overexpression enhances, whereas miR-106b depletion reduces CRC cell migration and invasion. Moreover, we identify DLC1 as a direct target of miR-106b, reveal its expression to be inversely correlated with miR-106b in CRC samples and show that its re-introduction reverses miR-106b-induced CRC cell migration and invasion. Furthermore, survival analyses showed the patients with high mi-106b/low DLC1 had shorter overall survival (OS) and disease-free survival (DFS) rates, and confirmed miR-106b may be an independent prognostic factor for OS and DFS in CRC patients.ConclusionsOur findings indicate that miR-106b promotes CRC cell migration and invasion by targeting DLC1. This miRNA may serve as a potential prognostic biomarker and therapeutic target for CRC.

BackgroundMicroRNAs (miRNAs) are small, non-coding RNAs that can function as oncogenes or tumor suppressors in human cancer. Abnormally expressed miR-224 was found to play a fundamental role in several types of cancer. The aim of this study was to investigate the prognostic and biological values of miR-224 in colorectal cancer (CRC).MethodsQuantitative RT-PCR (qRT-PCR) was used to evaluate expression levels of miR-224. The postoperative survival rate was analyzed with Kaplan–Meier method. The roles of miR-224 in cell proliferation, migration and invasion were analyzed with pre-miR-224 transfected cells. In addition, the regulation of SMAD4 by miR-224 was evaluated by qRT-PCR, Western blotting and luciferase reporter assays.ResultsIn the present study, we demonstrated that miR-224 was significantly up-regulated in CRC tissue samples and associated with disease relapse and a relative poorer disease-free survival rate. Moreover, ectopic expression of miR-224 potently promoted tumor cell proliferation, migration and invasion in vitro. Furthermore, the over-expression of miR-224 in CRC cell lines decreased SMAD4 expression at the translational level and decreased SMAD4-driven luciferase-reporter activity.ConclusionsOur data suggest that miR-224 could play an oncogenic role in the cellular processes of CRC and represent a novel biomarker for tumor relapse of CRC patients.

The increased expression of miR-183 is closely related to advanced clinical stage, lymph node and distant metastases, and poor prognosis of CRC, indicating that miR-183 may serve as a predictive biomarker for the prognosis or the aggressiveness of CRC.

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.