Guan Yaowu, Rao Zhongming, Chen Cheng
Department of Thoracic Surgery, Zhumadian Central Hospital, Zhumadian, Henan 463000, China.
Department of Radiotherapy, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu 210009, China.
Oncotarget. 2017 Dec 21;9(4):4924-4934. doi: 10.18632/oncotarget.23529. eCollection 2018 Jan 12.
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 and . 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.
Ⅲ类组蛋白去乙酰化酶沉默信息调节因子1（SIRT1）在包括肺癌在内的多种肿瘤中经常过度表达；然而，其调控机制在很大程度上尚不清楚。在本研究中，我们发现人肺癌组织中SIRT1蛋白水平与mRNA水平之间存在不一致的趋势，这表明转录后机制可能参与SIRT1的调控。由于微小RNA是基因表达的重要转录后调节因子，通过生物信息学分析获得了可能潜在结合SIRT1的候选微小RNA。我们通过评估miR-30a过表达或敲低后肺癌细胞中SIRT1的表达以及荧光素酶测定，进一步通过实验验证了SIRT1是miR-30a的直接靶点。此外，我们表明miR-30a通过抑制SIRT1抑制肺癌细胞的增殖、侵袭并促进其凋亡。综上所述，本研究确定了一个新的调控轴，其中miR-30a和SIRT1调节肺癌细胞的增殖、侵袭和凋亡以及肺肿瘤发生。
