Mifepristone regulates the multidrug resistance via miR-758/MEPE of Hela cell lines

Background:In cervical cancer, matrix extracellular phosphoglycoprotein (MEPE) plays an important role of multidrug resistance, which is associated with miR-758. Mifepristone has anti-drug resistance effects, but whether mifepristone regulates the expression of multidrug resistance proteins via the pathway mediated by miR-758/MEPE is still unclear. Hela cells were induced by mifepristone (named as Hela/MIF cells). Then, matrix extracellular phosphoglycoprotein siRNA, and miR-758 mimics were transfected into HeLa/MIF cells. The sensitivity, clone forming ability, migration, and level of apoptosis of the cells in each group were respectively measured by CCK-8 assays, clone forming assays, transwell assays, and flow cytometry analysis. The targeting of miR-758 to MEPE was verified by dual-luciferase assay. At last, the expression of MDR-1, MRP-1, and GST-π were detected by qPCR and western blot assays. Results: The induction by mifepristone not only decreased the sensitivity of Hela cells, but also up-regulated the expression of multidrug resistance proteins. On this basis, by increasing the expression of miR-758 or downregulating the expression of MEPE, the expression of multidrug resistance proteins decreased, while the sensitivity of Hela cells to mifepristone were improved and the level of Hela cells proliferation, colony forming, and invasion further decreased. Conclusions: The induction by mifepristone inhibited the proliferation of Hela cells, but the sensitivity of Hela cells increased. The mechanism may depend on the expression of multidrug resistance protein. This study shows that regulating the expression of miR-758 and MEPE can reduce the resistance of Hela cells to mifepristone, enhance the sensitivity, and further improve the inhibitory effect of mifepristone.

Cervical cancer; Multidrug resistance; Mifepristone; MicroRNA; matrix extracellular phosphoglycoprotein.

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