Knockdown of circ_0000285 in combination with X-ray irradiation affects the proliferation and apoptosis of cervical cancer cells
10.3760/cma.j.cn113030-20250108-00012
- VernacularTitle:敲低circ_0000285协同X射线照射影响宫颈癌细胞增殖及凋亡研究
- Author:
Yaru WANG
1
;
Changping QU
1
;
Dongli ZHANG
1
Author Information
1. 河南大学淮河医院妇产科，开封 475000
- Publication Type:Journal Article
- Keywords:
Uterine cervical neoplasms;
circ_0000285;
Radiotherapy;
Proliferation;
Apoptosis
- From:
Chinese Journal of Radiation Oncology
2025;34(10):1026-1032
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect and mechanism of circ_0000285 on regulating the proliferation and apoptosis of radiotherapy-resistant (RR) cells in cervical cancer.Methods:The RR cervical cancer cell lines HeLa-RR and SiHa-RR were constructed by gradually increasing the dose of X-ray irradiation. After transfection and/or 5 Gy X-ray irradiation, both HeLa-RR and SiHa-RR cells were divided into the control, si-circ_0000285, 5 Gy, si-circ_0000285+5 Gy, si-circ_0000285+miR-4731-5p inhibitor+5 Gy and si-circ_0000285+ miR-4731-5p inhibitor+si-FOXM1+5 Gy groups, respectively. Cell proliferation was detected using CCK-8 assay. The expression of circ_0000285 in cervical cancer cells HeLa and SiHa, as well as RR cervical cells HeLa-RR and SiHa-RR was measured by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). The targeting relationship between circ_0000285 and miR-4731-5p as well as the targeting relationship between miR-4731-5p and forkhead box M1 ( FOXM1) were assessed by dual-luciferase reporter gene assay. The expression of FOXM1 protein was detected by Western blot. Cell apoptosis was evaluated by flow cytometry. Results:CCK-8 assay confirmed the successful construction of radioresistant cervical cancer cells HeLa-RR and SiHa-RR. The expression of circ_0000285 in HeLa-RR and SiHa-RR cells was significantly higher than that in HeLa and SiHa cells. Dual-luciferase reporter gene assay showed that miR-4731-5p was the target gene of circ_0000285, and FOXM1 was the target gene of miR-4731-5p. Compared with the control group, the cell proliferation level of si-circ_0000285 group ( t=6.12, 9.80, P=0.004, 0.001) and si-circ_0000285+5 Gy group ( t=2.45,15.93, P=0.071, <0.001) in HeLa-RR and SiHa-RR cells were significantly decreased, and the apoptosis rate were significantly increased ( t=10.14, 17.78, P=0.001, <0.001; t=14.43, 31.44,both P<0.001). The cell proliferation ability of si-circ_0000285+5 Gy group in HeLa-RR and SiHa-RR cells was significantly higher than that of si-circ_0000285 group ( t=3.67, 6.12, P=0.021, 0.004), and the apoptosis rate was significantly higher than that in the si-circ_0000285 group ( t=8.96, 11.07, P=0.001, <0.001). Compared with the si-circ_0000285+5 Gy group, the proliferation ability of si-circ_0000285+miR-4731-5p inhibitor+5 Gy group in HeLa-RR and SiHa-RR cells was significantly decreased ( t=19.61, 12.25, both P<0.001), and the apoptosis rate was significantly decreased ( t=13.74, 29.78, both P<0.001). Compared with the si-circ_0000285+miR-4731-5p inhibitor+5 Gy group, the proliferation ability of si-circ_0000285+miR-4731-5p inhibitor+si-FOXM1+5 Gy group in HeLa-RR and SiHa-RR cells was significantly decreased ( t=2.45, 15.93, P=0.071, <0.001), and the apoptosis rate was significantly increased ( t=19.56, 35.71, both P<0.001). Conclusions:Knocking down circ_0000285 in combination with X-ray irradiation can significantly inhibit the proliferation of cervical cancer cells and promote cell apoptosis, and the mechanism may be that circ_0000285 regulates the miR-4731-5p/FOXM1 signaling axis.
