Human papillomavirus (HPV) infection and viral protein expression cause several epigenetic alterations that lead to cervical carcinogenesis. Our previous study identified that upregulated lysine-specific demethylase (KDM) 2 A promotes cervical cancer progression by inhibiting mircoRNA (miR)-132 function. However, the roles of histone methylation modifiers in HPV-related cervical cancer remain unclear. In the present study, changes in the expression of 48 histone methylation modifiers were assessed following knockdown of HPV16 E6/E7 in CaSki cells. The dysregulated expression of KDM5A was identified, and its function in cervical cancer was investigated in vitro and in vivo. E7 oncoprotein-induced upregulation of KDM5A promoted cervical cancer cell proliferation and invasiveness in vitro and in vivo, which was correlated with poor prognosis in patients with cervical cancer. KDM5A was found to physically interact with the promoter region of miR-424–5p, and to suppress its expression by removing the tri- and di-methyl groups from H3K4 at the miR-424–5p locus. Furthermore, miR-424–5p repressed cancer cell proliferation and invasiveness by targeting suppressor of zeste 12 (Suz12). KDM5A upregulation promoted cervical cancer progression by repressing miR-424–5p, which resulted in a decrease in Suz12. Therefore, KDM5A functions as a tumor activator in cervical cancer pathogenesis by binding to the miR-424–5p promoter and inhibiting its tumor-suppressive function. These results indicate a function for KDM5A in cervical cancer progression and suggest its candidacy as a novel prognostic biomarker and target for the clinical management of this malignancy.

人乳头瘤病毒（HPV）感染和病毒蛋白表达引起几种表观遗传学改变，导致宫颈癌变。我们先前的研究发现，赖氨酸特异性脱甲基酶（KDM）2 A上调通过抑制mircoRNA（miR）-132功能促进宫颈癌的进展。但是，组蛋白甲基化修饰剂在与HPV相关的宫颈癌中的作用仍不清楚。在本研究中，在敲除CaSki细胞中的HPV16 E6 / E7后，评估了48种组蛋白甲基化修饰剂的表达变化。KDM5A的失调表达被鉴定，并且其在宫颈癌功能进行了研究在体外和体内。E7癌蛋白诱导的KDM5A上调促进宫颈癌细胞的增殖和侵袭性体外和体内，这与子宫颈癌患者预后不良有关。发现KDM5A与miR-424-5p的启动子区域发生物理相互作用，并通过从miR-424-5p的位点上的H3K4去除三甲基和二甲基来抑制其表达。此外，miR-424-5p通过靶向zeste 12（Suz12）抑制剂来抑制癌细胞的增殖和侵袭性。KDM5A的上调通过抑制miR-424-5p促进宫颈癌的进展，从而导致Suz12减少。因此，KDM5A通过与miR-424-5p启动子结合并抑制其肿瘤抑制功能，在宫颈癌的发病机理中起着肿瘤激活剂的作用。