Abstract
microRNAs (miRNAs) function as oncogenes or tumor suppressors in human cancers by targeting mRNAs for degradation and/or translational repression. miR‐497 has been proposed as a tumor suppressive miRNA and its deregulation is observed in human cancers. However, the prognostic value of miR‐497 and its underlying molecular pathways involved in the initiation and development of hepatocellular carcinoma (HCC) are poorly investigated. In the present study, we found that the mean level of miR‐497 in HCC tissues was lower than that in adjacent nontumor tissues. Clinical data indicated that low expression of miR‐497 was prominently associated with adverse prognostic features of HCC including high serum alpha‐fetoprotein (AFP) level, large tumor size, high Edmondson–Steiner grading and advanced tumor–node–metastasis (TNM) stage. Furthermore, miR‐497 was an independent prognostic factor for indicating both 5‐year overall survival and disease‐free survival of HCC patients. Gain‐ and loss‐of‐function studies showed that miR‐497 reduced cell proliferation and induced apoptosis in HCC cells. Yes‐associated protein 1 (YAP1) was identified as a direct target of miR‐497 in HCC. An inverse correlation between YAP1 and miR‐497 expression was observed in HCC tissues. Notably, YAP1 knockdown abrogated the effects of miR‐497 deletion on HCC cells with decreased cell proliferation and increased apoptosis. In conclusion, we report that miR‐497 is a potent prognostic indicator and may suppress tumor growth of HCC by targeting YAP1.
Highlights
MicroRNAs function as oncogenes or tumor suppressors in human cancers by targeting messenger RNA (mRNA) for degradation and/or translational repression. miR-497 has been proposed as a tumor suppressive miRNA and its deregulation is observed in human cancers
We tested the expression of miR-497 in a retrospective cohort of 86 hepatocellular carcinoma (HCC) tissues and matched adjacent nontumor tissues using quantitative reverse transcription-PCR (qRT-PCR)
Tumors with low expression of miR-497 associated with shorter overall survival and disease-free survival of HCC patients (P < 0.05, respectively, Fig. 1B,C)
Summary
MicroRNAs (miRNAs) function as oncogenes or tumor suppressors in human cancers by targeting mRNAs for degradation and/or translational repression. miR-497 has been proposed as a tumor suppressive miRNA and its deregulation is observed in human cancers. MicroRNAs (miRNAs) function as oncogenes or tumor suppressors in human cancers by targeting mRNAs for degradation and/or translational repression. The prognostic value of miR-497 and its underlying molecular pathways involved in the initiation and development of hepatocellular carcinoma (HCC) are poorly investigated. Clinical data indicated that low expression of miR-497 was prominently associated with adverse prognostic features of HCC including high serum alpha-fetoprotein (AFP) level, large tumor size, high Edmondson–Steiner grading and advanced tumor–node–metastasis (TNM) stage. Yes-associated protein 1 (YAP1) was identified as a direct target of miR-497 in HCC. We report that miR-497 is a potent prognostic indicator and may suppress tumor growth of HCC by targeting YAP1. Abbreviations AFP, alpha-fetoprotein; FACS, fluorescence-activated cell sorting; FBS, fetal bovine serum; HCC, hepatocellular carcinoma; HRP, horseradish peroxidase; TNM, tumor–node–metastasis; YAP1, Yes-associated protein 1.
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