miR-101-3p sensitizes non-small cell lung cancer cells to irradiation.

miR-101-3p sensitizes non-small cell lung cancer cells to irradiation.
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DOI:
10.1515/med-2020-0044
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发表时间:
2020
期刊:
Open medicine (Warsaw, Poland)
影响因子:
--
通讯作者:
Zhang H
Zhang H
中科院分区:
其他
文献类型:
--
作者:
Li Z;Qu Z;Wang Y;Qin M;Zhang H

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近年来研究发现,microRNA调控非小细胞肺癌(NSCLC)的放射敏感性。本研究旨在探讨miR-101- 3 p与NSCLC放射敏感性的关系。根据我们的结果,miR-101- 3 p在NSCLC组织和细胞系中下调。此外,miR-101- 3 p在A549细胞对辐射的反应中以剂量依赖性方式降低。miR-101- 3 p的上调降低了辐射抗性细胞的存活分数和集落形成率,并增加了辐射诱导的凋亡,而miR-101- 3 p的缺失在辐射敏感细胞中具有相反的作用。此外,雷帕霉素的机制靶点(mTOR)是miR-101- 3 p的靶基因。miR-101- 3 p在A549 R细胞中的过表达抑制了mTOR、p-mTOR和p-S6的表达,而在A549细胞中,miR-101- 3 p的抑制增强了这种抑制。有趣的是,mTOR的升高减轻了miR-101- 3 p上调诱导的辐射抗性细胞系中辐射敏感性的增加。相比之下,雷帕霉素破坏了miR-101- 3 p介导的辐射敏感性细胞系中辐射敏感性的降低。此外,miR-101- 3 p过表达增强了NSCLC异种移植小鼠模型中的放射疗效。总之,miR-101- 3 p通过抑制mTOR信号通路使A549细胞对辐射敏感。
Recent studies have revealed that microRNAs regulate radiosensitivity of non-small cell lung cancer (NSCLC). The aim of this study was to investigate whether miR-101-3p is correlated with radiosensitivity of NSCLC. According to our results, miR-101-3p was downregulated in NSCLC tissues and cell lines. Moreover, miR-101-3p was decreased in A549 cells’ response to irradiation in a dose-dependent manner. Upregulation of miR-101-3p decreased survival fraction and colony formation rate and increased irradiation-induced apoptosis in irradiation-resistant cells, while miR-101-3p depletion had the opposite effects in irradiation-sensitive cells. Furthermore, mechanistic target of rapamycin (mTOR) is a target gene of miR-101-3p. The expressions of mTOR, p-mTOR, and p-S6 were curbed by overexpression of miR-101-3p in A549R cells, which was enhanced by repression of miR-101-3p in A549 cells. Intriguingly, elevation in mTOR abated miR-101-3p upregulation-induced increase in irradiation sensitivity in irradiation-resistant cell line. In contrast, rapamycin undermined miR-101-3p inhibitor-mediated reduction of irradiation sensitivity in irradiation-sensitive cell line. Besides, miR-101-3p overexpression enhanced the efficacy of radiation in an NSCLC xenograft mouse model. In conclusion, miR-101-3p sensitized A549 cells to irradiation via inhibition of mTOR-signaling pathway.
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