circLPAR3靶向miR-1238对食管癌细胞放射敏感性的影响

doi:10.3760/cma.j.cn113030-20200919-00473

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Abstract Objective To evaluate the effect of circLPAR3 on the radiosensitivity of esophageal cancer cells and investigate its mechanism. Methods The cancer tissues and and adjacent tissues of 37 patients with esophageal cancer were collected, and esophageal cancer cell lines Eca-109, EC9706 and KYSE30 and esophageal epithelial cells HET-1A were cultured in vitro. The expression levels of circLPAR3 and miR-1238 in the tissues and cells were measured by RT-qPCR. Eca-109 cells were transfected with circLPAR3siRNA and miR-1238 mimics or co-transfected with circLPAR3siRNA and miR-1238 inhibitor. Cell cloning experiment was conducted to evaluate the effects of silencing circLPAR3, overexpressing miR-1238, or silencing both circLPAR3 and miR-1238 on the radiosensitivity of Eca-109 cells. After Eca-109 cells that silenced circLPAR3, overexpressed miR-1238 or silenced both circLPAR3 and miR-1238 were exposed to 4Gy irradiation, CCK-8 assay (A value), flow cytometry and Western blot were employed to assess the effects of silencing circLPAR3, overexpressing miR-1238, or silencing both circLPAR3 and miR-1238 combined with 4Gy irradiation on the proliferation and apoptosis of Eca-109 cells and the expression levels of CyclinD1, p21, Bcl-2 and Bax proteins. Dual luciferase reporter gene experiment and RNA pull down experiment were performed to verify the regulatory relationship between circLPAR3 and miR-1238. Results Compared with adjacent tissues, the expression level of circLPAR3 was up-regulated in the esophageal cancer tissues (P<0.05), while that of miR-1238 was down-regulated (P<0.05). Compared with HET-1A cells, the expression levels of circLPAR3 were up-regulated in the esophageal cancer cell lines Eca-109, EC9706 and KYSE30(all P<0.05), whereas those of miR-1238 were down-regulated (all P<0.05). Silencing circLPAR3 or overexpressing miR-1238 reduced the survival fraction of Eca-109 cells (all P<0.05), and the sensitization ratio was 1.21 and 1.75, respectively. Silencing circLPAR3 or overexpressing miR-1238decreased the A value of Eca-109 cells and the expression levels of CyclinD1 and Bcl-2 proteins (all P<0.05), while increased the apoptosis rate of Eca-109 cells and the expression levels of p21 and Bax proteins (all P<0.05). After silencing circLPAR3 or overexpressing miR-1238 combined with 4Gy irradiation, the A value of Eca-109 cells and the expression levels of CyclinD1 and Bcl-2 proteins were decreased (all P<0.05), while Eca-109 cell apoptosis rate and the expression levels of p21 and Bax proteins were increased (all P<0.05). circLPAR3 targeted and negatively regulated the expression level of miR-1238 in Eca-109 cells. After silencing miR-1238 and circLPAR3simultaneously, the survival fraction of Eca-109 cells was higher than that when only silencing circLPAR3, and the sensitization ratio was 0.59. Silencing miR-1238 reversed the effects of silencing circLPAR3 combined with 4Gy irradiation on the proliferation and apoptosis of Eca-109 cells. Conclusion circLPAR3 is highly expressed in esophageal cancer tissues and cell lines, and silencing the expression of circLPAR3 can inhibit the proliferation of esophageal cancer Eca-109 cells, promote their apoptosis, and enhance cell radiosensitivity by up-regulating miR-1238.

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	Yuan Xiaosun
	Zhang Lei
	Rao Shilei
	Zhang Kai
	Ma Huili
	Li Changsheng
	Zhang Jingwei
	Ren Zhonghai

Key words： circLPAR3 gene miR-1238 gene Cell proliferation Cell apoptosis Radiosensitivity Esophageal cancer tissue Esophageal cancer cell line

Received: 19 September 2020

Cite this article:

Yuan Xiaosun,Zhang Lei,Rao Shilei et al. Effect of circLPAR3 on radiosensitivity of esophageal cancer cells by targeting miR-1238[J]. Chinese Journal of Radiation Oncology, 2022, 31(1): 71-78.

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http://journal12.magtechjournal.com/Jweb_fszlx/EN/10.3760/cma.j.cn113030-20200919-00473 OR http://journal12.magtechjournal.com/Jweb_fszlx/EN/Y2022/V31/I1/71

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