The role of ubiquitin-specific protease 22 in the pathogenesis of PCOS
Objective:To explore the role and mechanism of ubiquitin-specific protease 22(USP22)in the pathogenesis of PCOS.Methods:A PCOS model was established using dehydroepiandrosterone(DHEA)-induced mice,and the expression changes of USP22 in the ovarian tissues of PCOS mice and control mice were detected by immunohistochemistry and Western blot.A total of 500 nmol/L dihydrotestosterone(DHT)was added to the ovarian granulosa cell line(KGN)cells to simulate the state of Kaohsiung.And the siRNA targeting USP22 was constructed to knock down the expression of USP22 in KGN cells.Blank siRNA was added to the control group.CCK-8 was used to detect the proliferative changes of the cells in each group,reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the mRNA expression level of cell cycle-related molecules,and western blot technique was used to detect the expression of cell cycle-related proteins and signaling pathway-related proteins.Results:USP22 protein was mainly located in the nucleus of granulosa cells,and the expression of USP22 in ovarian tissues of PCOS mice was significantly lower than that of normal mice.The results of cellular experiments showed that knockdown of USP22 could decrease the proliferation of KGN cells significantly(P＜0.05),the results of RT-PCR and Western Blot showed that the mRNA and protein expression levels of Cyclin Bl,Cyclin D1 and Cyclin El were significantly decreased(P＜0.05).When DHT was added at the same time as knockdown USP22 in KGN cells,the proliferation ability and related molecule expression of KGN cells decreased significantly(P＜0.05).Moreover,after knockdown of USP22,the expression levels of signaling pathway-related proteins,p-PI3K and p-AKT,were significantly decreased in KGN cells(P＜0.05).Conclusions:USP22 regulates the proliferation of KGN cells through the PI3K/AKT signaling pathway,resulting in the influence on the pathogenesis of PCOS.
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