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Long non-coding RNA MEG3 regulates proliferation and apoptosis in non-small cell lung cancer via the miR-205-5p/LRP1 pathway

机译:长的非编码RNA MEG3通过miR-205-5p / LRP1途径 调节非小细胞肺癌的增殖和凋亡

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Long non-coding RNA (lncRNA) MEG3 has been identified as a tumor suppressor in various cancers including non-small cell lung cancer (NSCLC). However, its molecular mechanisms in the development and progression of NSCLC have not been thoroughly elucidated until now. Here, we identified that the expression levels of MEG3 and miR-205-5p were respectively down-regulated and up-regulated in human NSCLC tissues and cells. Bioinformatics analysis, luciferase reporter assays, and RNA immunoprecipitation (RIP) assays combined with western blot assays further validated that MEG3 inhibited miR-205-5p expression via direct interaction. Function and mechanism analysis revealed that the exogenous expression of MEG3 hindered proliferation and induced apoptosis by acting as a miR-205-5p sponge to enhance low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) expression in NSCLC. Moreover, a transplantation experiment demonstrated that MEG3 exerted an oncosuppressive effect via the miR-205-5p/LRP1 axis. Taken together, our study demonstrates that MEG3 represses tumorigenesis through regulating the miR-205-5p/LRP1 pathway in NSCLC.
机译:长非编码RNA(lncRNA)MEG3已被鉴定为包括非小细胞肺癌(NSCLC)在内的各种癌症的肿瘤抑制因子。但是,到目前为止,尚不清楚其在NSCLC发生和发展中的分子机制。在这里,我们发现在人NSCLC组织和细胞中,MEG3和miR-205-5p的表达水平分别被下调和上调。生物信息学分析,荧光素酶报告基因分析和RNA免疫沉淀(RIP)分析与蛋白质印迹分析相结合,进一步验证了MEG3通过直接相互作用抑制了miR-205-5p表达。功能和机制分析表明,MEG3的外源表达通过充当miR-205-5p海绵来增强NSCLC中低密度脂蛋白(LDL)受体相关蛋白1(LRP1)的表达而阻止了增殖并诱导了细胞凋亡。此外,移植实验表明,MEG3通过miR-205-5p / LRP1轴 发挥了抑癌作用。两者合计,我们的研究表明,MEG3通过调节NSCLC中的miR-205-5p / LRP1途径抑制肿瘤发生。

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