MicroRNA‐450b‐3p inhibits cell growth by targeting phosphoglycerate kinase 1 in hepatocellular carcinoma

Dysregulation of microRNAs frequently contributes to the occurrence and progression of human diseases, including hepatocellular carcinoma (HCC). In this study, the role of miR‐450b‐3p in HCC was investigated. Gene Expression Omnibus database and HCC specimens were used to evaluate the expression lev...

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Veröffentlicht in:Journal of cellular biochemistry 2019-11, Vol.120 (11), p.18805-18815
Hauptverfasser: Chen, Zide, Zhuang, Wenhang, Wang, Zeju, Xiao, Weiliang, Don, Wei, Li, Xianming, Chen, Xiaoming
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Sprache:eng
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Zusammenfassung:Dysregulation of microRNAs frequently contributes to the occurrence and progression of human diseases, including hepatocellular carcinoma (HCC). In this study, the role of miR‐450b‐3p in HCC was investigated. Gene Expression Omnibus database and HCC specimens were used to evaluate the expression level of miR‐450b‐3p and the patient's prognosis. Cell functional analyses and tumor xenograft model were used to assess the role of miR‐450b‐3p in HCC. Bioinformatics was used to predict the downstream target gene of miR‐450b‐3p, which was verified by dual‐luciferase reporter assay. MiR‐450b‐3p was found to be downregulated in HCC cell lines and tissues, compared with nontransformed immortal hepatic cells and adjacent normal liver tissues, respectively. Lower expression of miR‐450b‐3p was associated with poor overall survival and disease‐free survival in patients with HCC. Ectopic expression of miR‐450b‐3p inhibited HCC cell viability, colony formation, and cell‐cycle progression in vitro, and suppressed the growth of HCC xenograft tumors in vivo. Interestingly, a negative correlation between miR‐450b‐3p and phosphoglycerate kinase 1 (PGK1) protein was observed among HCC specimens. Additionally, miR‐450b‐3p inhibited PGK1 expression and phosphorylation of protein kinase B in HCC cell lines. Further experiments confirmed that PGK1 was a direct target of miR‐450b‐3p. Moreover, restoration of PGK1 abrogated the inhibitory effect of miR‐450b‐3p on HCC proliferation and cell division. In conclusion, miR‐450b‐3p is downregulated in human HCC and exerts tumor suppressive effects at least in part by inhibiting PGK1. MiR‐450b‐3p is underexpressed in hepatocellular carcinoma (HCC) tissues. MicroRNA‐450b‐3p inhibits cell proliferation and division of HCC cells. GPK1 is a direct downstream target of miR‐450b‐3p.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.29196