MiR-92b targets p57kip2 to modulate the resistance of hepatocellular carcinoma (HCC) to ionizing radiation (IR) -based radiotherapy
MiR-92b targets p57kip2 to modulate the resistance of hepatocellular carcinoma (HCC) to ionizing radiation (IR) -based radiotherapy
复制标题
MiR-92b 靶向 p57kip2 调节肝细胞癌 (HCC) 对电离辐射 (IR) 放疗的抵抗力
DOI：
10.1016/j.biopha.2018.11.080
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发表时间：
2019
影响因子：
7.5
通讯作者：
金晶
中科院分区：
文献类型：
--
作者：
王健仰;金晶
肝细胞癌（HCC）是最常见的消化系统恶性肿瘤之一。由于对放疗的抵抗，HCC患者的预后较差。根据之前的研究和在线工具预测，我们假设据报道可促进 HCC 细胞增殖的 miR-92b 可能与众所周知的肿瘤抑制因子 p57kip2 结合，从而调节 HCC 对电离辐射 (IR) 放疗的放射抗性。在本研究中，观察到 HCC 组织和细胞系中 miR-92b 表达较高； miR-92b 高表达与 HCC 患者较差的预后相关。 miR-92b的过表达通过促进癌细胞增殖、减弱细胞凋亡和消除IR诱导的G2/M期细胞周期来增强HCC对IR治疗的放射抗性。 miR-92b通过直接结合p57kip2的3′-UTR，负向调节p57kip2的蛋白水平； miR-92b抑制增强了IR对HCC细胞的细胞作用，这种作用可以通过p57kip2敲低来减弱，换句话说，miR-92b通过p57kip2调节HCC对IR放疗的放射抗性。综上所述，miR-92b抑制HCC组织和细胞系中p57kip2的表达，从而增强HCC对基于IR的放疗的放射抗性；靶向 miR-92b 来挽救 HCC 中的 p57kip2 表达可能有助于对基于 IR 的放射治疗敏感的 HCC 细胞。
Hepatocellular carcinoma (HCC) is one of the most common digestive system malignant tumors. Due to the resistance to radiotherapy, the prognosis in patients with HCC is poor. Based on previous studies and online tools prediction, we hypothesized that miR-92b, which was reported to promote HCC cell proliferation, might bind to p57kip2, a well-known tumor suppressor, to modulate the radioresistance of HCC to ionizing radiation (IR) -based radiotherapy. In the present study, a higher miR-92b expression in HCC tissues and cell lines was observed; a high miR-92b expression was correlated with poorer prognosis in patients with HCC. The overexpression of miR-92b enhanced the radioresistance of HCC to IR treatment by promoting cancer cell proliferation, attenuating cell apoptosis and remove IR-induced cell cycle at G2/M phase. Through directly binding to the 3′-UTR of p57kip2, miR-92b negatively regulated the protein levels of p57kip2; miR-92b inhibition enhanced the cell effect of IR on HCC cells, which could be attenuated by the p57kip2 knockdown, in other words, miR-92b modulated the radioresistance of HCC to IR-based radiotherapy through p57kip2. Taken together, miR-92b inhibits p57kip2 expression in HCC tissues and cell lines, thus enhancing the radioresistance of HCC to IR-based radiotherapy; targeting miR-92b to rescue p57kip2 expression in HCC might help sensitive HCC cells to IR-based radiotherapy.