A novel microRNA identified in hepatocellular carcinomas is responsive to LEF1 and facilitates proliferation and epithelial-mesenchymal transition via targeting of NFIX.
2018
Hepatocellular carcinoma (
HCC) is one of the most prevalent cancers. It has been demonstrated that various cellular microRNAs (miRNAs) play an important role in
HCCdevelopment. Here, we analyzed the miRNA profile in
HCCtissues by Solexa sequencing, and we identified a novel microRNA, miR-HCC1, which is upregulated in
HCCtissues. Further experiments showed that miR-HCC1 promoted
HCCcell proliferation in vivo and in vitro, and migration and invasion resulting from the
epithelial-mesenchymal transition(EMT) process.
Nuclear factor I/X (
NFIX), which inhibited cell proliferation, migration and invasion in
HCCcells, was identified as a direct and functional target of miR-HCC1. Furthermore,
lymphoid enhancer binding factor 1(LEF1), a transcription factor, was shown to bind the promoter of miR-HCC1 and activate its expression. Collectively, these results indicate that LEF1-upregulated miR-HCC1 functions as an oncogene through the negative regulation of
NFIXexpression, which links the LEF1/miR-HCC1/
NFIXaxis to contribute to cell proliferation, migration and invasion of
HCCcells and could provide novel insights into miRNA function and hepatocarcinogenesis and potential biomarkers for
HCC.
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