miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma.
miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma.
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miR-93 作为 oncomiR 下调胃癌中 PDCD4
DOI：
10.1038/srep23772
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发表时间：
2016-03-29
影响因子：
4.6
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Liang H;Wang F;Chu D;Zhang W;Liao Z;Fu Z;Yan X;Zhu H;Guo W;Zhang Y;Guan W;Chen X
程序性细胞死亡4（PDCD 4）作为一种抑癌基因，在包括胃癌在内的多种肿瘤中经常被下调。以往的研究表明PDCD 4通过调控细胞凋亡参与肿瘤发生，但这一过程的分子基础尚未完全阐明，也没有研究表明该基因在胃癌中的上游调控。在这项研究中，我们使用生物信息学分析来寻找可能靶向PDCD 4的miRNAs，并将miR-93确定为候选者。此外，我们观察到在人胃癌组织中miR-93和PDCD 4蛋白水平之间的负相关性，而不是mRNA水平。我们通过评估miR-93过表达或敲低后胃癌细胞中PDCD 4的表达，进一步实验验证了PDCD 4是miR-93的直接靶点。此外，通过miR-93靶向PDCD 4的生物学后果使用细胞凋亡测定法在体外进行了检查。我们证明，通过miR-93抑制PDCD 4抑制胃癌细胞的凋亡。最后，我们揭示了miR-93通过负调节PDCD 4促进异种移植小鼠胃肿瘤生长的发展。综上所述，本研究的发现表明miR-93通过靶向PDCD 4在胃癌肿瘤发生中的致癌作用，特别是在细胞凋亡中。
Programmed cell death 4 (PDCD4), as a tumor suppressor gene, is frequently reduced in a variety of tumors, including gastric cancer. Previous findings have indicated that PDCD4 participates in tumorigenesis through the regulation of apoptosis, but the molecular basis of this process has not been fully elucidated and no studies have shown the upstream regulation of this gene in gastric cancer. In this study, we used bioinformatics analysis to search for miRNAs that could potentially target PDCD4 and identified miR-93 as a candidate. Moreover, we observed the inverse correlation between miR-93 and PDCD4 protein levels, but not mRNA levels, in human gastric cancer tissues. We further experimentally validated PDCD4 as the direct target of miR-93 by evaluating PDCD4 expression in gastric cancer cells after the overexpression or knockdown of miR-93. Additionally, the biological consequences of targeting PDCD4 through miR-93 were examined using cell apoptosis assaysin vitro. We demonstrated that the repression of PDCD4 through miR-93 suppressed the apoptosis of gastric cancer cells. Finally, we revealed that miR-93 promoted the development of gastric tumor growth in xenograft mice by negatively regulating PDCD4. Taken together, the findings of the present study indicated the oncogenic role of miR-93 in gastric cancer tumorigenesis through targeting PDCD4, particularly in apoptosis.