MicroRNA-148a-3p enhances sensitivity of radiotherapy of lung adenocarcinoma cells by targeting core 1β13-galactosyltransferase 1
Objective To investigate the expression and clinical significance of microRNA-148a-3p(miR-148a-3p)in lung adenocarcinoma and analyze the effect and mechanism of miR-148a-3p on ra-diotherapy sensitivity of lung adenocarcinoma cells by targeting the protein core 1 β13-galactosyltrans-ferase 1(C1GALT1).Methods Seventy-six patients'tumor tissues from lung adenocarcinoma tissue microarrays and lung adenocarcinoma A549 cell line were selected for the study.The miR-148a-3p in situ hybridizations(ISH)and C1GALT1 immunohistochemical staining were performed on the tissue microarrays to analyze the correlations of miR-148a-3p expression with clinical pathology,prognosis and C1GALT1 expression in the tumor tissues of the 76 patients with lung adenocarcinoma.A549 cells were transfected with miR-148a-3p overexpression plasmid by using cell transfection technique;the clone formation assay was used to detect the sensitivity of the transfected cells for radiotherapy after re-ceiving 2 Gy radiotherapy;the protein expression level of cellular C1GALT1 was detected by western blot;the targeted regulatory relationship between miR-148a-3p and C1GALT1 was verified by dual-luciferase reporter gene experiment;the mechanism of miR-148a-3p regulating the sensitivity of A549 cells to radiotherapy was analyzed by co-transfection technique.Results Low expression of miR-148a-3p in 76 cases of lung adenocarcinoma tissues was significantly associated with lymph node metastasis(P=0.012);the prognosis of patients with high expression of miR-148a-3p was significantly better than that of patients with low expression of miR-148a-3p(P=0.005);there was a significant negative correlation between the expression of miR-148a-3p and C1GALT1 in lung adenocarcinoma tissues(P=0.023).Multivariate analysis showed that low expression of miR-148a-3p,T staging and lymph node metastasis were the independent risk factors for prognosis.Clone formation experiment showed that the number of clone formation in the miR-148a-3p overexpression group was significantly lower than that in the control group(P＜0.001);western blot result showed that overexpression of miR-148a-3p was able to significantly down-regulate the level of C1GALT1 protein in cells(P＜0.001).Dual luciferase reporter gene experiment showed that miR-148a-3p was able to regulate the expression of C1GALT1 by binding to the 3'UTR of C1GALT1.Functional rescue experiment showed that C1GALT1 could partially offset the radiosensitization effect of miR-148a-3p.Conclusion Low ex-pression of miR-148a-3p in lung adenocarcinoma is significantly associated with lymph node metasta-sis,high expression of C1GALT1 and poor prognosis,and miR-148a-3p can enhance the radiosensitiv-ity of lung adenocarcinoma cells by negatively regulating the expression of C1GALT1.
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维普
