miR-16 promotes the apoptosis of human cancer cells by targeting FEAT.
miR-16 promotes the apoptosis of human cancer cells by targeting FEAT.
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miR-16通过靶向FEAT促进人类癌细胞凋亡
DOI：
10.1186/s12885-015-1458-8
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发表时间：
2015-06-02
期刊：
影响因子：
3.8
通讯作者：
Zhou G
中科院分区：
文献类型：
--
作者：
Liang H;Fu Z;Jiang X;Wang N;Wang F;Wang X;Zhang S;Wang Y;Yan X;Guan WX;Zhang CY;Zen K;Zhang Y;Chen X;Zhou G
背景尽管人类癌症具有改变的癌基因的异质性组合，但在大多数癌症中，一些关键基因普遍失调。其中一个这样的基因，FEAT（在正常组织中微弱表达，在肿瘤中异常过表达），在多种人类癌症中均匀过表达，并通过抑制细胞凋亡在肿瘤发生中起重要作用。然而，精确的分子机制，通过FEAT是上调在肿瘤generation.MethodsIn这项研究中，我们使用生物信息学分析，寻找潜在的目标FEAT的miRNA仍然在很大程度上是未知的。我们通过western blotting检测FEAT蛋白水平，通过qRT-PCR检测miR-16水平。建立miR-16上调和FEAT沉默的癌细胞系（A549、MCF-7和Huh-7），并在体外评估对癌细胞凋亡的影响。结果在FEAT的3′-非翻译区（3′-UTR）发现了miR-16的特异性靶位点。与生物信息学分析一致，我们确定了肺癌、乳腺癌和肝细胞癌组织中miR-16和FEAT蛋白水平之间的负相关性。然后，我们使用细胞转染和荧光素酶测定实验验证miR-16作为FEAT的直接调节剂。最后，我们证明了FEAT的抑制miR-16促进了癌细胞的凋亡。ConclusionsOur研究结果提供了第一个线索，关于miR-16作为肿瘤抑制因子在癌细胞中通过抑制FEAT翻译的作用。
BackgroundAlthough human cancers have heterogeneous combinations of altered oncogenes, some crucial genes are universally dysregulated in most cancers. One such gene,FEAT(faint expression in normal tissues, aberrant overexpression in tumors), is uniformly overexpressed in a variety of human cancers and plays an important role in tumorigenesis by suppressing apoptosis. However, the precise molecular mechanism through which FEAT is upregulated during tumorigenesis remains largely unknown.MethodsIn this study, we used bioinformatic analyses to search for miRNAs that potentially target FEAT. We examined the expression of FEAT protein level by western blotting and miR-16 level by qRT-PCR assay. Cancer cell lines (A549, MCF-7 and Huh-7) with miR-16 upregulation and FEAT silencing were established and the effects on apoptosis of cancer cellsin vitrowere assessed. Luciferase reporter assay was also performed to investigate the interaction between miR-16 and FEAT.ResultsWe identified a specific target site for miR-16 in the 3′-untranslated region (3′-UTR) of FEAT. Consistent with the bioinformatic analyses, we identified an inverse correlation between the miR-16 and FEAT protein levels in lung cancer, breast cancer, and hepatocellular cancer tissues. We then experimentally validated miR-16 as a direct regulator of FEAT using cell transfection and luciferase assays. Finally, we demonstrated that the repression of FEAT by miR-16 promoted the apoptosis of cancer cells.ConclusionsOur findings provide the first clues regarding the role of miR-16 as a tumor suppressor in cancer cells through the inhibition of FEAT translation.
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