Background: Colorectal cancer (CRC) remains to be one of the most common malignancies worldwide. Various studies have demonstrated that microRNAs (miRs) play a critical role in regulating cancer progression and sensitivity to chemoradiotherapy. miR-1 was found to be aberrantly expressed in CRC. However, it has not been fully elucidated whether miR-1 regulated CRC cell radioresistance. Methods: The expression of miR-1 was detected using quantitative real-time polymerase chain reaction in CRC tissues and cell lines. Colony survival and proliferation were determined using colony formation assay and MTT assay, respectively. Apoptosis and levels of related proteins, Bax and Bcl-2, were detected using flow cytometer assay and western blotting analysis. Migration and invasion were measured using wound healing assay and transwell invasion assay. The levels of invasion-associated proteins, E-cadherin, MMP2 and MMP9, were detected using western blotting analysis. Results: miR-1 was found to be downregulated in CRC tissues and cell lines compared with adjacent normal tissues. In vitro, miR-1 overexpression significantly suppressed colony survival and proliferation, and induced cell apoptosis under irradiation, but no apoptosis was detected without irradiation. Furthermore, miR-1 mimics promoted the expression of Bax and E-cadherin and decreased the expression of Bcl-2, MMP2 and MMP9, and apparently impaired the invasion and migration of CRC cells in synergy with radiotherapy. Conclusion: miR-1 enhanced the radiosensitivity of CRC cells by inducing cell apoptosis and the synergic inhibition of aggressive phenotypes, which may serve as a promising therapeutic target for CRC patients.
Aim. The aim of our work was to determine the utility of DNM1 as a biomarker for the diagnosis and prognosis of colon cancer (CC). Methods. DNM1 expression variations in CC vs. normal tissues were investigated using The Cancer Genome Atlas (TCGA) database. The association of DNM1 expression levels with the clinicopathological variables in CC prognosis was investigated using logistic regression analyses. Independent prognostic factors for CC were evaluated using univariate and multivariate Cox regression analyses. The correlation between DNM1 expression and immune cell infiltration was estimated using single-sample Gene Set Enrichment Analysis (ssGSEA). Results. DNM1 expression in CC tissues was significantly higher than that in normal tissues. High DNM1 expression was significantly correlated with M stage, N stage, perineural invasion and lymphatic invasion and predicted poor prognosis. The univariate analysis highlighted that DNM1 was an independent CC risk factor. Results of ssGSEA showed that DNM1 was linked to several cancer-related pathways, including the neuroactive ligand-receptor interaction, hypertrophic cardiomyopathy, ECM-receptor interaction, dilated cardiomyopathy, and calcium signaling pathway. Moreover, DNM1 expression was positively correlated with the level of infiltration by Neutrophils, Tregs, NK cells, and Macrophages. Conclusion. DNM1 has a significant function and has diagnostic and prognostic potential for CC.
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