Circ_0026134 regulates the miR-1270/GRB2 pathway to affect the radiosensitivity of hepatoma cells
10.3760/cma.j.cn501113-20231129-00250
- VernacularTitle:circ_0026134调控miR-1270/GRB2途径影响肝癌细胞的放射敏感性
- Author:
Xiaoyang ZHAO
1
;
Yuyan LIU
;
Lupeng LI
;
Jianwen LIU
Author Information
1. 河南省人民医院 郑州大学人民医院综合介入科，郑州 450000
- Keywords:
Liver cancer;
Cell proliferation;
Apoptosis;
Migration and invasion;
Radio-sensitivity;
circular _0026134;
Micro RNA1270;
Growth factor receptor binding prot
- From:
Chinese Journal of Hepatology
2024;32(1):40-48
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate whether circular RNA 0026134 (circ_0026134) affects the radiosensitivity of hepatoma cells by regulating the miR-1270/growth factor receptor-bound protein 2 (GRB2) pathway.Methods:Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of circ_0026134, miR-1270, and GRB2 in liver cancer tissues and cells. Bioinformatics analysis, a dual-luciferase gene reporter assay, RT-qPCR, and western blot were used to analyze the targeting relationships between circ_0026134 and miR-1270 and miR-1270 and GRB2. The effects of circ_0026134, miR-1270, and GRB2 expression combined with 6 Gy on the proliferation, invasion, migration, and apoptosis of Huh7 and SK-HEP-1 cells were detected by a cell counting kit, a transwell assay, a scratch assay, and flow cytometry. The tumorigenesis experiment was used to detect the effect of silencing circ_0026134 in nude mice. Measurement data are expressed as the mean ± standard deviation. The independent sample t-test was used for comparison between two groups, and the one-way analysis of variance and SNK- q test were used for comparison between multiple groups. P < 0.05 was considered statistically significant. Results:The expression levels of circ_0026134 and GRB2, Huh7, and SK-HEP-1 cells in liver cancer tissues were significantly increased, while the expression levels of miR-1270 were significantly decreased ( P < 0.05). The expression of circ_0026134 in Huh7 and SK-HEP-1 decreased significantly after radiotherapy ( P < 0.05). circ_0026134 binds directly to miR-1270 and negatively regulates miR-1270 expression ( P < 0.05). miR-1270 binds directly to GRB2 and negatively regulates GRB2 expression ( P < 0.05). 6 Gy radiation significantly inhibited the proliferation, migration, and invasion of Huh7 and SK-HEP-1 cells and induced apoptosis ( P < 0.05). Silencing circ_0026134 or overexpression of miR-1270 significantly enhanced the anti-proliferation, anti-migration, invasion, and pro-apoptosis effects of 6 Gy treatment on hepatoma cells ( P < 0.05). Inhibition of miR-1270 significantly weakened the effects of silencing circ_0026134 combined with 6 Gy radiation on proliferation, migration, invasion, and apoptosis of hepatoma cells ( P < 0.05). Overexpression of GRB2 significantly weakened the effects of miR-1270 overexpression combined with 6 Gy radiation on proliferation, migration, invasion, and apoptosis of hepatoma cells ( P < 0.05). circ_0026134 knockdown significantly delayed tumor growth in vivo ( P < 0.05). Conclusion:Silencing circ_0026134 strengthens radiation treatment’s anti-proliferation, anti-migration, invasion, and pro-apoptotic effects in hepatoma cells by negatively regulating the miR-1270/GRB2 pathway, thereby enhancing radiosensitivity.
