Department of Interventional Radiology, The Fifth People's Hospital of Jinan, Jinan, 250000 Shandong, China.
Department of Minimally Invasive Intervention, Ganzhou People's Hospital, Ganzhou, Jiangxi 341000, China.
Comput Math Methods Med. 2022 Oct 10;2022:1450098. doi: 10.1155/2022/1450098. eCollection 2022.
The relationship between tumor suppressor gene miR-302a-3p and radiotherapy for hepatocellular carcinoma (HCC) remains unclear. This study intended to illustrate the molecular mechanism how miR-302a-3p regulated radiotherapy sensitivity of HCC.
miR-302a-3p expression in HCC tissues and cells was examined by qRT-PCR. The effect of miR-302a-3p on HCC radiotherapy sensitivity were detected by CCK-8, colony formation, and flow cytometry assays. The expression levels of cell cycle-related proteins were detected by Western blot. The influence of miR-302a-3p on radiotherapy sensitivity of HCC was further investigated via cell cycle inhibitor (Caudatin) treatment. The target gene (MCL1) of miR-302a-3p was obtained by bioinformatics analysis, and their binding relationship was confirmed by RNA-binding protein immunoprecipitation assay. The mechanisms of miR-302a-3p regulating cell cycle and affecting radiotherapy sensitivity of HCC cells through MCL1 were further explored through the rescue experiments.
miR-302a-3p expression was remarkably reduced in radiotherapy-resistant tissues and cells of HCC. miR-302a-3p overexpression restored sensitivity of radiotherapy-resistant HCC cells to radiotherapy. Treatment with cell cycle inhibitor Caudatin could reverse suppressive effect of miR-302a-3p downregulation on sensitivity of HCC to radiotherapy. Additionally, miR-302a-3p could restrain MCL1 expression. cell assays further revealed that miR-302a-3p/MCL1 axis could enhance radiotherapy sensitivity of HCC cells by inducing G0/G1 arrest.
miR-302a-3p facilitated radiotherapy sensitivity of HCC cells by regulating cell cycle via MCL1, which provided a new underlying target for radiotherapy resistance of HCC patients.
抑癌基因 miR-302a-3p 与肝细胞癌（HCC）的放射治疗之间的关系尚不清楚。本研究旨在阐明 miR-302a-3p 调节 HCC 放射治疗敏感性的分子机制。
通过 qRT-PCR 检测 HCC 组织和细胞中 miR-302a-3p 的表达。通过 CCK-8、集落形成和流式细胞术检测 miR-302a-3p 对 HCC 放射治疗敏感性的影响。通过 Western blot 检测细胞周期相关蛋白的表达水平。通过细胞周期抑制剂（Caudatin）处理进一步研究 miR-302a-3p 对 HCC 放射治疗敏感性的影响。通过生物信息学分析获得 miR-302a-3p 的靶基因（MCL1），并通过 RNA 结合蛋白免疫沉淀实验证实它们的结合关系。通过挽救实验进一步探讨了 miR-302a-3p 通过 MCL1 调节细胞周期并影响 HCC 细胞放射治疗敏感性的机制。
miR-302a-3p 在 HCC 放射抵抗组织和细胞中的表达显著降低。miR-302a-3p 的过表达恢复了对放射抵抗 HCC 细胞的放射治疗敏感性。用细胞周期抑制剂 Caudatin 处理可逆转 miR-302a-3p 下调对 HCC 放射敏感性的抑制作用。此外，miR-302a-3p 可以抑制 MCL1 的表达。细胞实验进一步表明，miR-302a-3p/MCL1 轴通过诱导 G0/G1 期阻滞增强 HCC 细胞的放射治疗敏感性。
miR-302a-3p 通过调节 MCL1 来促进 HCC 细胞的放射治疗敏感性，为 HCC 患者的放射治疗抵抗提供了新的潜在靶点。
