MicroRNA-30e-5p suppresses non-small cell lung cancer tumorigenesis by regulating USP22-mediated Sirt1/JAK/STAT3 signaling
MicroRNA-30e-5p suppresses non-small cell lung cancer tumorigenesis by regulating USP22-mediated Sirt1/JAK/STAT3 signaling
复制标题
MicroRNA-30e-5p通过调节USP22介导的Sirt1/JAK/STAT3信号传导抑制非小细胞肺癌肿瘤发生
DOI：
10.1016/j.yexcr.2017.11.027
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发表时间：
2018-01-15
影响因子：
3.7
通讯作者：
Ding, Fangbao
中科院分区：
文献类型：
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作者：
Xu, Gaojun;Cai, Jie;Ding, Fangbao
MicroRNA-30e-5p （miR-30e-5p）是一种已知在非小细胞肺癌（NSCLC）中下调的肿瘤抑制因子。然而，miR-30e-5p如何抑制NSCLC肿瘤发生尚不清楚。泛素特异性肽酶22 （USP22）在NSCLC中表达上调，并通过Sirtl-JAK-STAT3通路促进肿瘤发生。在这项研究中，我们研究了miR-30e-5p是否通过靶向USP22在NSCLC中抑制肿瘤生长。我们的研究结果显示，在NSCLC组织中，miR-30e-5p的表达与USP22呈负相关。荧光素酶报告基因检测显示，miR-30e-5p通过结合3'UTR中的特定序列负调控USP22的表达。MiR-30e-5p过表达和USP22敲低在体内显著抑制肿瘤生长，在体外诱导非小细胞肺癌细胞周期阻滞和凋亡。miR-30e-5p的抑制作用可通过USP22敲低来阻止。MiR-30e-5p抑制SIRT1表达，增加p53和STAT3磷酸化形式（pSTAT3）的表达。此外，miR-30e-5p阻止了usp22介导的SIRT1、pSTAT3和p53表达的调节。综上所述，这些发现表明miR-30e-5p通过下调usp22介导的Sirtl/JAK/STAT3信号通路抑制NSCLC的肿瘤发生。我们的研究已经确定miR-30e-5p是治疗NSCLC的潜在治疗靶点。
MicroRNA-30e-5p (miR-30e-5p) is a tumor suppressor that is known to be downregulated in non-small cell lung cancer (NSCLC). However, how miR-30e-5p inhibits NSCLC tumorigenesis is not known. Ubiquitin-specific peptidase 22 (USP22) is upregulated in NSCLC and promotes tumorigenesis via a Sirtl-JAK-STAT3 pathway. In this study, we investigated whether miR-30e-5p inhibits tumor growth by targeting USP22 in NSCLC. Our results reveal that miR-30e-5p expression was correlated negatively with USP22 in NSCLC tissues. Luciferase reporter assays showed that miR-30e-5p negatively regulated USP22 expression by binding to a specific sequence in the 3'UTR. MiR-30e-5p overexpression and USP22 knockdown significantly inhibited tumor growth in vivo and induced cell cycle arrest and apoptosis in NSCLC cells in vitro. The effects of miR-30e-5p inhibition were prevented by USP22 knockdown. MiR-30e-5p inhibited SIRT1 expression and increased expression of p53 and the phosphorylated form of STAT3 (pSTAT3). Furthermore, miR-30e-5p prevented USP22-mediated regulation of SIRT1, pSTAT3, and p53 expression. Taken together, these findings suggest that miR-30e-5p suppresses NSCLC tumorigenesis by downregulatingUSP22-mediated Sirtl/JAK/STAT3 signaling. Our study has identified miR-30e-5p as a potential therapeutic target for the treatment of NSCLC.