MicroRNA-148a-3p enhances sensitivity of radiotherapy of lung adenocarcinoma cells by targeting core 1β13-galactosyltransferase 1
- VernacularTitle:微小RNA-148a-3p靶向核心1β13-半乳糖基转移酶1增强肺腺癌细胞的放疗敏感性的研究
- Author:
Lin SHEN
1
;
Yue REN
;
Yizhou DENG
;
Xudong YIN
;
Yong CHEN
Author Information
- Publication Type:Research Article
- Keywords: microRNA-148a-3p; core 1β13-galactosyltransferase 1; lung adenocarcinoma; radiotherapy sensitivity; prognosis
- From: Journal of Clinical Medicine in Practice 2024;28(6):1-8
- CountryChina
- Language:Chinese
-
Abstract:
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 radiotherapy sensitivity of lung adenocarcinoma cells by targeting the protein core 1β13-galactosyltransferase 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 receiving 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 expression of miR-148a-3p in lung adenocarcinoma is significantly associated with lymph node metastasis, high expression of C1GALT1 and poor prognosis, and miR-148a-3p can enhance the radiosensitivity of lung adenocarcinoma cells by negatively regulating the expression of C1GALT1.
