miR-30a suppresses lung cancer progression by targeting SIRT1.

miR-30a suppresses lung cancer progression by targeting SIRT1.
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DOI:
10.18632/oncotarget.23529
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发表时间:
2018-01-12
期刊:
影响因子:
--
通讯作者:
Chen C
Chen C
中科院分区:
其他
文献类型:
--
作者:
Guan Y;Rao Z;Chen C

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III类组蛋白去乙酰化酶沉默信息调节因子1(SIRT 1)经常在多种肿瘤中过表达,包括肺癌;然而,其调节机制在很大程度上是未知的。在本研究中,我们发现SIRT 1蛋白和mRNA在人肺癌组织中的表达趋势不一致,提示SIRT 1的调控可能涉及转录后机制。由于microRNA是基因表达的重要转录后调节因子,因此通过生物信息学分析获得了可能与SIRT 1结合的候选miRNAs。我们通过评估miR-30 a过表达或敲低后肺癌细胞中SIRT 1的表达以及荧光素酶测定,进一步实验验证了SIRT 1是miR-30 a的直接靶点。此外,我们发现miR-30 a通过抑制SIRT 1在体外和体内抑制肺癌细胞的增殖、侵袭和促进凋亡。总之,这项研究确定了一个新的调节轴,其中miR-30 a和SIRT 1调节肺癌细胞的增殖,侵袭和凋亡以及肺肿瘤发生。
The class III histone deacetylase silent information regulator 1 (SIRT1) is frequently overexpressed in a variety of tumors, including lung cancer; however, its regulatory mechanisms are largely unknown. In this study, we found that an inconsistent trend between SIRT1 protein and mRNA levels in human lung cancer tissues, suggesting that a post-transcriptional mechanism may involved in SIRT1 regulation. Because microRNAs are important post-transcriptional regulators of gene expression, candidate miRNAs that could potentially bind SIRT1 were gained through bioinformatics analyses. We further experimentally validated SIRT1 as the direct target of miR-30a by evaluating SIRT1 expression in lung cancer cells after the overexpression or knockdown of miR-30a and by luciferase assay. Moreover, we showed that miR-30a inhibited proliferation, invasion and promoted apoptosis of lung cancer cells by inhibiting SIRT1 in vitro and in vivo. Taken together, this study identified a new regulatory axis in which miR-30a and SIRT1 regulate the proliferation, invasion and apoptosis of lung cancer cells and lung tumorigenesis.
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