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MicroRNA-450b-3p inhibits cell growth by targeting phosphoglycerate kinase 1 in hepatocellular carcinoma
Authors:Zide Chen  Wenhang Zhuang  Zeju Wang  Weiliang Xiao  Wei Don  Xianming Li  Xiaoming Chen
Institution:1. Department of Radiation Oncology, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China

Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China

Hepatology Unit, Nanfang Hospital, Guangzhou, China;2. Department of Interventional Radiology, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Provincial Academy of Medical Sciences, Guangzhou, China;3. School of Chemistry, Sun Yat-sen University, Guangzhou, China;4. Department of Interventional Radiology, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China;5. Hepatic Surgery Center, Tongji Hospital, Wuhan, China;6. Department of Radiation Oncology, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China

Abstract: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.
Keywords:cell cycle  cell proliferation  hepatocellular carcinoma  miR-450b-3p  phosphoglycerate kinase 1
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