Abstract
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 cells in vitro were 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1458-8) contains supplementary material, which is available to authorized users.
Highlights
Human cancers have heterogeneous combinations of altered oncogenes, some crucial genes are universally dysregulated in most cancers
In this study, we experimentally investigated the direct regulation of FEAT by miR-16 and the biological role of miR-16 targeting FEAT in human cancer cells
After measuring the protein levels of FEAT in these cancer tissues and the corresponding noncancerous tissues, we found that FEAT protein is dramatically overexpressed in cancer tissues but totally absent in normal tissues (Fig. 1a)
Summary
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. Oncogenes that contribute to the development of human cancers are highly variable among different types of cancer and among individual tumors of the same type [1, 2] It is still poorly understood whether there are crucial oncogenes that are commonly altered in diverse cancers. Gene expression profiling has suggested that FEAT drives receptor tyrosine kinase and hedgehog signaling pathways
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