BackgroundColorectal carcinoma (CRC) is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs, miRs) play important roles in carcinogenesis. MiR-32 has been shown to be upregulated in CRC. In this study, we identified the potential effects of miR-32 on some important biological properties of CRC cells, and clarified the regulation of PTEN by miR-32.MethodsThe effect of miR-32 on PTEN expression was assessed in CRC cell lines with miR-32 mimics/inhibitor to increase/decrease miR-32 expression. Furthermore, the roles of miR-32 in regulating CRC cells biological properties were analyzed with miR-32 mimics/inhibitor-transfected cells. The 3′-untranslated region (3′-UTR) of PTEN combined with miR-32 was verified by dual-luciferase reporter assay.ResultsGain-of-function and loss-of-function studies showed that overexpression of miR-32 promoted SW480 cell proliferation, migration, and invasion, reduced apoptosis, and resulted in downregulation of PTEN at a posttranscriptional level. However, miR-32 knock-down inhibited these processes in HCT-116 cells and enhanced the expression of PTEN protein. In addition, we further identified PTEN as the functional downstream target of miR-32 by directly targeting the 3′-UTR of PTEN.ConclusionsOur results demonstrated that miR-32 was involved in tumorigenesis of CRC at least in part by suppression of PTEN.

MicroRNA-126 (miR-126) has been reported to be a tumor suppressor that targets CXCR4 in colorectal cancer (CRC) cells. This study investigated whether miR-126 has any prognostic impact in patients with CRC. MiR-126 and CXCR4 mRNA expression in 92 pairs of CRC and adjacent nontumorous tissues was examined using quantitative real-time PCR, and CXCR4 protein expression was assessed by immunohistochemistry (IHC) and Western blotting. The correlation between miR-126 and CXCR4 protein expression and clinicopathological features and overall survival rate was determined. MiR-126 was downregulated in CRC tissues that expressed high levels of CXCR4 mRNA. IHC and Western blotting detected high expression of CXCR4 protein in CRC tissues. An inverse correlation was observed between miR-126 and CXCR4 protein expression in CRC tissues. Moreover, low miR-126 and high CXCR4 protein expression was associated with distant metastasis, clinical TNM stage, and poor survival. Multivariate analysis indicated that miR-126 was an independent prognostic factor for overall survival, suggesting its clinical significance as a prognostic predictor in CRC patients.

MicroRNAs (miRNAs, miRs) play important roles in pathogenesis and development of human diseases, including malignancy. Some may affect tumor progression through targeting tumor suppressor genes. MiR-135b has been shown to be upregulated in CRC. In this study, we evaluated the role of miR-135b in colorectal cancer (CRC) and its regulatory role for metastasis suppressor-1 (MTSS1) and its mechanisms. The levels of miR-135b and MTSS1 gene expression in 35 CRC and corresponding cancer-adjacent tissues, 27 colorectal adenoma, and 16 normal tissue samples were quantified using qRT-PCR and western blot analysis. The effect of miR-135b on MTSS1 expression was assessed by miR-135b mimics or inhibitor transfection to deregulate miR-135b expression. The direct interaction between them was verified by 3'-UTR dual-luciferase reporter assay. Furthermore, the roles of miR-135b in regulating CRC cells migration and invasion properties were analyzed with miR-135b mimics or inhibitor-transfected cells and silenced expression of MTSS1 in miR-135b inhibitor transfected cells. CRC tissues showed significantly upregulated miR-135b expression and reduced MTSS1 expression. High miR-135b levels were significantly associated with lymph node and distant metastasis. The miR-135b inhibitor decreased miR-135b expression and caused MTSS1 upregulation at the post-transcriptional level. However, overexpression of miR-135b caused MTSS1 protein downregulation. The 3'-UTR of MTSS1 harbored a binding site for miR-135b. Finally, miR-135b inhibitor-transfected cells exhibited markedly reduced cell migration and invasive abilities, and this effect could be reversed by MTSS1-siRNA. Our results demonstrated that miR-135b downregulated MTSS1 expression and contributed to CRC cell invasion, indicating its involvement in CRC progression.

MicroRNAs (miRNAs, miRs) are suspected to play important roles in carcinogenesis. MiR-32 has altered expression in colorectal cancer (CRC); however, the clinical significance of miR-32 expression in the process of carcinogenesis is poorly understood. In this study, we determined the levels of, the correlation between, and the clinical significance of the expression of miR-32 and phosphatase and tensin homologue (PTEN), a tumor suppressor targeted by miR-32, in CRC. The levels of miR-32 and PTEN gene expression in 35 colorectal carcinoma samples, 35 corresponding cancer-adjacent tissue samples, 27 colorectal adenoma samples, and 16 normal tissue samples were quantified using real-time quantitative reverse transcriptase-polymerase chain reaction. PTEN protein expression was determined using western blot and immunohistochemistry (IHC). The relationship between the miR-32 and PTEN protein expression and clinicopathological factors was analyzed. Significant upregulation of miR-32 expression and reduction of PTEN were identified in CRC tissues. High miR-32 levels were significantly associated with lymph node and distant metastasis, and Kaplan-Meier analysis indicated that patients with high miR-32 expression had a poor overall survival. Low PTEN protein expression was also significantly correlated with distant metastasis. An inverse relationship between miR-32 and PTEN protein expression was identified. In addition, IHC analysis revealed weak or indiscernible PTEN staining in tumor tissue. MiR-32 overexpression was correlated with specific CRC clinicopathological features and may be a marker of poor prognosis in CRC patients. MiR-32 and PTEN expression were inversely correlated, and miR-32 may be associated with the development of CRC.

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