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  • br Fig Downregulation of p kip partially


    Fig. 5. Downregulation of p27kip1 partially reversed the phenotypes of si-ZNF692 cells. (A) The transfection efficiency of si-p27kip1 was determined by qRT-PCR. (B–D) The proliferative abilities were partially rescued after treatment with si-p27kip1 in si-ZNF692 HeLa cells. (E) Knockdown of p27kip1 partially reversed the inhibitory effect of si-ZNF692 on the migration and invasion of HeLa cells. (F) Western blotting showed that the GW311616 of p27kip1 and PThr160-CDK2 were partially recovered after knockdown of p27kip1 in si-ZNF692 compared with si-ZNF692 alone in HeLa cells. Error bars represent the mean ± SD values of three independent experiments. *P b 0.05, **P b 0.01, ***P b 0. 001.
    Fig. 6. Knockdown of ZNF692 inhibited tumour growth in vivo. (A–B) The transfection efficiency of sh-ZNF692 was determined by qRT-PCR and Western blotting. (C) A total of eight nude female mice were sacrificed and xenograft tumours were collected 4 weeks after injection. (D-E) Tumour volume and weight were decreased in the sh-ZNF692 group compared with those in the sh-NC group. (F) The expression of ZNF692, Ki-67 was downregulated and p27kip1 was upregulated in sh-ZNF692 xenograft tumours as analysed by IHC staining. Error bars represent the mean ± SD values. *P b 0.05, **P b 0.01, ***P b 0.001.
    of p27kip1 have been widely studied in CC [34,35]. Many studies have also indicated that p27kip1 can suppress CDK2-Thr160 phosphorylation [36,37]. Stephanie Mueller et al. [38] found a key mechanism for the ad-justment of the G1/S transition via CDK2 phosphorylation at Thr160 in hepatocytes. Our data coincide with preceding studies, showing that si-ZNF692 induces G1 phase arrest by regulating the p27kip1 expression. The expression of p27kip1, a cell cycle-dependent kinase inhibitor
    (CDKI), was up-regulated in si-ZNF692 cells, to induce G1 phase arrest accompanied by the down-regulation of PThr160-CDK2 in si-ZNF692 
    cells. Meanwhile, decreased p27kip1 and increased PThr160-CDK2 were observed in oe-ZNF692 cells.
    The imbalance of p27 expression in cancer has mainly been contrib-uted to proteasomal degradation [39–41]; however, little is known of its disordered expression at the transcription level is little known. Re-cently, Yawei Li et al. proved that expression of p27 can be transcrip-tionally upregulated by FOXO1 directly binding to its promoter [42]. Our results showed that si-ZNF692 inhibited proliferation, migration, invasion and G1 phase processes in CC cells mainly by increasing
    p27kip1 expression. The rescue experiments indicated that knockdown of p27kip1 partially recovered the phenotypes in si-ZNF692 HeLa cells. ChIP assay and luciferase reporter assay indicated that ZNF692 directly bound the promoter region of p27kip1 at 815-1022 bp to suppress its transcription. Therefore, ZNF692 might have carcinogenic effects par-tially in a p27kip1-dependent manner. In conclusion, we found that ZNF692 is overexpressed in CC and is positively correlated with advanced TNM stage and lymph node metas-tasis. It plays an important role in CC progression by promoting the pro-liferation, invasion and migration of CC cells. With regard to the
    underlying mechanism, ZNF692 could enhance the cell cycle transition by regulating the p27kip1/PThr160-CDK2 signal pathway. Moreover,
    ZNF692 directly binds to the promoter region (815-1022 bp) of p27kip1 to exert its effect on promoting CC aggressiveness. Our present study adds to the accumulating evidence that ZNF692 exerts a carcino-genic role in CC and could be a potential prognostic biomarker as well as a target for treatment of CC.
    Supplementary data to this article can be found online at https://doi.