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Human papillomavirus type 16 E7 oncoprotein-induced upregulation of lysine-specific demethylase 5A promotes cervical cancer progression by regulating the microRNA-424–5p/suppressor of zeste 12 pathway
- Source :
- Experimental Cell Research. 396:112277
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- 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.
- Subjects :
- Adult
0301 basic medicine
Papillomavirus E7 Proteins
Uterine Cervical Neoplasms
Mice
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Cell Movement
Cell Line, Tumor
Histone methylation
microRNA
medicine
SUZ12
Animals
Humans
Epigenetics
Cell Proliferation
Cervical cancer
Human papillomavirus 16
Mice, Inbred BALB C
biology
Papillomavirus Infections
Epithelial Cells
Cell Biology
medicine.disease
Xenograft Model Antitumor Assays
Neoplasm Proteins
Tumor Burden
MicroRNAs
030104 developmental biology
Gene Expression Regulation
Lymphatic Metastasis
030220 oncology & carcinogenesis
KDM5A
Host-Pathogen Interactions
Disease Progression
biology.protein
Cancer research
Demethylase
Female
Retinoblastoma-Binding Protein 2
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 00144827
- Volume :
- 396
- Database :
- OpenAIRE
- Journal :
- Experimental Cell Research
- Accession number :
- edsair.doi.dedup.....c4e00543a817dedfb43da886e114cd31