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研究 miR-95 基因敲减对非小细胞肺癌放射敏感性的影响。

Examining the effect of gene reduction in miR-95 and enhanced radiosensitivity in non-small cell lung cancer.

机构信息

Department of Respiratory, Huaihe Hospital of Henan University, Kaifeng, China.

出版信息

Cancer Gene Ther. 2016 Feb-Mar;23(2-3):66-71. doi: 10.1038/cgt.2016.2. Epub 2016 Feb 26.

Abstract

MicroRNAs (miRNAs) represent a group of novel therapeutic small molecules involved in the management of lung cancer treatment. Our study aims to investigate the potential role of miRNAs in the treatment of non-small cell lung cancer (NSCLC). Human miRNA microarray was performed in 60 recurrent NSCLC patient tissue samples following radiotherapy and their adjacent normal tissues. miRNA profiling results were validated using quantitative real-time PCR. Inner cell radiosensitivity and endogenous miRNA expression was determined by colony-formation assay and RT-PCR. We determined the effect of miRNA on cell proliferation, survival and metastasis; tumor xenografts were taken to identify the presence of miRNA in vivo. miRNA panel results indicated that a total of 14 miRNAs were differentially expressed in the recurrent NSCLC samples. In our study, miRNA-95 was highly overexpressed in recurrent NSCLC cells. Knockdown of miRNA-95 expression increased the radiosensitivity of NSCLC, promoted tumor cell apoptosis and decreased cellular proliferation. In vivo assays demonstrated reduced tumor growth and resistance to radiation in tumor xenografts by downregulating miRNA-95. Our study demonstrated a potential therapeutic measure of miRNA-95 as a radiosensitive marker for the treatment of non-small lung cancer.

摘要

微小 RNA(miRNAs)是一组新型的治疗性小分子,参与肺癌治疗的管理。我们的研究旨在探讨 miRNAs 在非小细胞肺癌(NSCLC)治疗中的潜在作用。在 60 例接受放疗后的复发性 NSCLC 患者组织样本及其相邻正常组织中进行了人类 miRNA 微阵列分析。使用定量实时 PCR 验证 miRNA 谱分析结果。通过集落形成试验和 RT-PCR 测定细胞内放射敏感性和内源性 miRNA 表达。我们确定了 miRNA 对细胞增殖、存活和转移的影响;进行肿瘤异种移植以鉴定 miRNA 在体内的存在。miRNA 谱结果表明,在复发性 NSCLC 样本中共有 14 种 miRNA 表达差异。在我们的研究中,miRNA-95 在复发性 NSCLC 细胞中高度过表达。下调 miRNA-95 表达可增加 NSCLC 的放射敏感性,促进肿瘤细胞凋亡,减少细胞增殖。体内实验表明,通过下调 miRNA-95,肿瘤异种移植中的肿瘤生长和对辐射的抵抗力降低。我们的研究表明,miRNA-95 作为一种放射敏感标志物,具有治疗非小细胞肺癌的潜在治疗措施。

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