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Overexpression of microRNA-9 enhances cisplatin sensitivity in hepatocellular carcinoma by regulating EIF5A2-mediated epithelial-mesenchymal transition.
- Source :
-
International journal of biological sciences [Int J Biol Sci] 2020 Jan 16; Vol. 16 (5), pp. 827-837. Date of Electronic Publication: 2020 Jan 16 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- We investigated the role of microRNA (miR)-9 in modulating chemoresistance in hepatocellular carcinoma (HCC) cells. MiR-9 was overexpressed or knocked down in HCC cell lines. Cell viability, cell proliferation, the expression of EIF5A2 and the epithelial-mesenchymal transition (EMT)-related proteins were examined. HCC cells overexpressing miR-9 were more sensitive to cisplatin; miR-9 knockdown yielded the opposite result. The in vivo nude mouse HCC xenograft tumors yielded the same results. EIF5A2 was identified as a potential target of miR-9, where miR-9 regulated EIF5A2 expression at mRNA and protein level. EIF5A2 knockdown reversed miR-9 inhibition-mediated cisplatin resistance. Altering miR-9 and EIF5A2 expression changed E-cadherin and vimentin expression. Furthermore, EIF5A2 mediated miR-9 EMT pathway regulation, indicating that miR-9 can enhance cisplatin sensitivity by targeting EIF5A2 and inhibiting the EMT pathway. Targeting miR-9 may be useful for overcoming drug resistance in HCC.<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.<br /> (© The author(s).)
- Subjects :
- Animals
Carcinoma, Hepatocellular genetics
Cell Line, Tumor
Cell Movement drug effects
Cell Movement ethics
Cell Proliferation drug effects
Cell Proliferation genetics
Epithelial-Mesenchymal Transition genetics
Epithelial-Mesenchymal Transition physiology
Female
Gene Expression Regulation, Neoplastic drug effects
Gene Expression Regulation, Neoplastic genetics
Humans
Immunohistochemistry
In Situ Nick-End Labeling
Liver Neoplasms genetics
Mice
Mice, Nude
MicroRNAs genetics
Peptide Initiation Factors genetics
RNA, Messenger genetics
RNA, Messenger metabolism
RNA-Binding Proteins genetics
Eukaryotic Translation Initiation Factor 5A
Carcinoma, Hepatocellular drug therapy
Carcinoma, Hepatocellular metabolism
Cisplatin therapeutic use
Liver Neoplasms drug therapy
Liver Neoplasms metabolism
MicroRNAs metabolism
Peptide Initiation Factors metabolism
RNA-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1449-2288
- Volume :
- 16
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- International journal of biological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 32071552
- Full Text :
- https://doi.org/10.7150/ijbs.32460