Abstract | BACKGROUND: METHODS: The expression of miR-3609 and EPAS-1 was examined by qPCR. Lentiviral particles containing the full-length sequences of miR-3609 (pri-miR-3609) were prepared. The antitumor effect of antitumor agents was examined by the in vitro and in vivo assays. RESULTS: The expression of miR-3609 was negatively correlated with that of EPAS-1 in both HCC clinical specimens and paired non- tumor specimens, and the effect of miR-3609 on the expression of EPAS-1 was confirmed by Western blot experiments. Overexpression of miR-3609 decreased the expression of EPAS-1 and, in turn, repressed the activation of the PXR pathway. miR-3609 decreased the transcription factor activation of PXR, repressed its recruitment to its target gene promoter regions, and decreased the expression of its target genes CYP3A4 and P-GP. In addition, miR-3609 decelerated the metabolism and clearance of sorafenib in HCC cells and enhanced the antitumor effect of sorafenib in HCC cells. CONCLUSION: Therefore, the results indicate that miR-3609 decreases the expression of EPAS-1 and enhances the sensitivity of HCC cells to sorafenib.
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Authors | Qing-Ping Shao, Chen Wei, Jie Yang, Wen-Zhou Zhang |
Journal | OncoTargets and therapy
(Onco Targets Ther)
Vol. 13
Pg. 7213-7227
( 2020)
ISSN: 1178-6930 [Print] New Zealand |
PMID | 32801751
(Publication Type: Journal Article)
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Copyright | © 2020 Shao et al. |