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首页> 外文期刊>Journal of experimental & clinical cancer research : >Radiation-induced miR-208a increases the proliferation and radioresistance by targeting p21 in human lung cancer cells
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Radiation-induced miR-208a increases the proliferation and radioresistance by targeting p21 in human lung cancer cells

机译:辐射诱导的miR-208a通过靶向人肺癌细胞中的p21来增加增殖和放射抵抗力

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摘要

Lung cancer has long been the most dangerous malignant tumor among males in both well developed and poorly developed countries. Radiotherapy plays a critical role in the curative management of inoperable non-small cell lung cancer (NSCLC) and is also used as a post-surgical treatment in lung cancer patients. Radioresistance is an important factor that limits the efficacy of radiotherapy for NSCLC patients. Increasing evidence suggests that microRNAs (miRNAs) possess diverse cellular regulatory roles in radiation responses. In this study, we used miRNA microarray technology to identify serum miRNAs that were differentially expressed before and after radiotherapy in lung cancer patients. We further examined the biological function of miR-208a on cell viability, apoptotic death and cell cycle distribution in human lung cancer cells and explored the probable mechanism. Nine miRNAs, including miR-29b-3p, miR-200a-3p, and miR-126-3p were significantly down-regulated, whereas miR-208a was the only miRNA that was up-regulated in the serum of the patients after radiation treatment (P?
机译:在发达和欠发达国家中,长期以来,肺癌一直是男性中最危险的恶性肿瘤。放射疗法在不可手术的非小细胞肺癌(NSCLC)的治疗中起着至关重要的作用,还被用作肺癌患者的术后治疗。放射抵抗是限制NSCLC患者放射疗法疗效的重要因素。越来越多的证据表明,microRNA(miRNA)在辐射反应中具有多种细胞调节作用。在这项研究中,我们使用miRNA芯片技术鉴定了肺癌患者放疗前后差异表达的血清miRNA。我们进一步检查了miR-208a对人肺癌细胞中细胞活力,凋亡死亡和细胞周期分布的生物学功能,并探讨了可能的机制。九种miRNA,包括miR-29b-3p,miR-200a-3p和miR-126-3p被显着下调,而miR-208a是放射治疗后患者血清中唯一被上调的miRNA。 (P≤0.05)。 X射线照射可诱导肺癌细胞中miR-208a的表达。 miR-208a的强制表达通过靶向p21促进肺癌细胞中AKT / mTOR途径的激活,从而促进细胞增殖并诱导放射抵抗,而miR-208a的下调则产生相反的作用。此外,miR-208a的下调增加了细胞凋亡的百分比,并抑制了NSCLC细胞中的G1期阻滞。此外,来自肺癌患者血清外泌体部分的miR-208a可能以时间依赖性方式穿梭至A549细胞,这可能有助于随后的生物学效应。本研究提供的证据表明,miR-208a可以通过靶向p21来影响人肺癌细胞的增殖和放射敏感性,并且可以被外来体转运。因此,miR-208a可以作为肺癌患者的潜在治疗靶标。

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