Wang Yunjiang, Du Jia
Department of Neurosurgery, Yancheng Third People's Hospital, Yancheng City, Jiangsu Province, 224001, China.
Cancer Center, Daping Hospital, Army Medical University, No. 10 Changjiang Zhilu, Daping Yuzhong District, Chongqing, 400042, China.
Open Life Sci. 2021 Nov 2;16(1):1175-1181. doi: 10.1515/biol-2021-0117. eCollection 2021.
Glioma is a type of common intracranial tumor. In this study, we investigated the molecular mechanism by which miR-378a-3p regulates cisplatin (CDDP) chemosensitivity in glioma cells via insulin-like growth factor 1 receptor (IGF1R). U251/CDDP cells were treated with CDDP and transfected with miR-378a-3p mimics, NC mimics, or pcDNA-IGF1R. qRT-PCR was used to measure the differential level of miR-378a-3p. CCK-8 assay was used to test cell proliferation, and flow cytometry was used to analyze apoptosis. The targeting relationship between miR-378a-3p and IGF1R was tested through a dual-luciferase reporter gene assay. In contrast to normal glial cells, the miR-378a-3p level decreased in human glioma U251 cells and had lower expression in U251/CDDP cells. Compared with the CDDP group, miR-378a-3p significantly caused the inhibition of U251/CDDP cell proliferation and enhanced apoptosis in the miR-378a-3p mimics + CDDP group. Another experiment confirmed that IGF1R was a target gene of miR-378a-3p, and overexpression of miR-378a-3p inhibited IGF1R expression. In addition, co-overexpression of miR-378a-3p and IGF1R induced the upregulation of the U251/CDDP cell proliferation and the inhibition of apoptosis in the miR-378a-3p mimics + pcDNA-IGF1R + CDDP group. This study confirmed that miR-378a-3p promoted the sensitivity of glioma cells to CDDP in glioma patients via targeting IGF1R to increase the therapeutic effect during chemotherapy.
胶质瘤是一种常见的颅内肿瘤。在本研究中，我们调查了miR-378a-3p通过胰岛素样生长因子1受体（IGF1R）调节胶质瘤细胞顺铂（CDDP）化疗敏感性的分子机制。用CDDP处理U251/CDDP细胞，并转染miR-378a-3p模拟物、NC模拟物或pcDNA-IGF1R。采用qRT-PCR检测miR-378a-3p的差异水平。采用CCK-8法检测细胞增殖，流式细胞术分析细胞凋亡。通过双荧光素酶报告基因检测验证miR-378a-3p与IGF1R的靶向关系。与正常神经胶质细胞相比，人胶质瘤U251细胞中miR-378a-3p水平降低，且在U251/CDDP细胞中表达更低。与CDDP组相比，在miR-378a-3p模拟物+CDDP组中，miR-378a-3p显著抑制U251/CDDP细胞增殖并增强细胞凋亡。另一实验证实IGF1R是miR-378a-3p的靶基因，miR-378a-3p过表达抑制IGF1R表达。此外，在miR-378a-3p模拟物+pcDNA-IGF1R+CDDP组中，miR-378a-3p与IGF1R共过表达诱导U251/CDDP细胞增殖上调并抑制细胞凋亡。本研究证实，miR-378a-3p通过靶向IGF1R促进胶质瘤患者胶质瘤细胞对CDDP的敏感性，从而提高化疗疗效。
