Serine/threonine kinases 31(STK31) may be a novel cellular target gene for the HPV16 oncogene E7 with potential as a DNA hypomethylation biomarker in cervical cancer

Autor: Chengquan Zhao, Xiao-Hui Xu, Xiao Yu, Xiao-Ning Bi, Yankui Wang, Ning Wang, Bing Luo, You-Lin Wang, Fu-Fen Yin
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Adult
Human papillomavirus
viruses
Papillomavirus E7 Proteins
Blotting
Western
Uterine Cervical Neoplasms
Biology
Protein Serine-Threonine Kinases
5-aza-2′deoxycytidine
Real-Time Polymerase Chain Reaction
03 medical and health sciences
Exon
0302 clinical medicine
Virology
Cell Line
Tumor
medicine
Biomarkers
Tumor
STK31
Humans
Promoter Regions
Genetic
Genetics
Human papillomavirus 16
DNA methylation
Oncogene
Human papillomavirus 18
Research
Gene Expression Profiling
Cancer
Promoter
Methylation
Biomarker
DNA
Oncogene Proteins
Viral
Middle Aged
medicine.disease
Gene expression profiling
DNA-Binding Proteins
030104 developmental biology
Infectious Diseases
Real-time polymerase chain reaction
030220 oncology & carcinogenesis
Host-Pathogen Interactions
Cancer research
Cervical cancer
Female
Zdroj: Virology Journal
ISSN: 1743-422X
Popis: Background Cervical cancer (CC) is a leading cause of mortality in females, especially in developing countries. The two viral oncoproteins E6 and E7 mediate the oncogenic activities of high-risk human papillomavirus (hrHPV), and hrHPV, especially HPV16 or/and HPV18 (HPV16/18) play critical roles in CC through different pathways. STK31 gene of which the expression has been proven to be regulated by the methylation status of its promoter, is one of the novel cancer/testis (CT) genes and plays important roles in human cancers. Reasearches have indicated that viral infection is correlated to the methylation statuses of some genes. Herein, we detected methylation status of the STK31 gene in cervical tumors and explored its interaction with HPV16 or/and HPV18 (HPV16/18) infection. Methods Bisulfite genomic sequencing PCR (BGS) combined with TA clone, methylation-specific PCR (MSP) were used to analyze methylation statuses of the STK31 gene promoter/exon 1 region in HPV16/18-positive, HPV-negative CC cell lines; ectopically expressed HPV16 E6, -E7, and -E6/E7 CC cells; normal cervical tissues and cervical tumor tissues of different stages. The mRNA and protein expressions of STK31 were detected by RT-PCR and western blotting. Results The STK31 gene promoter/exon 1 was hypomethylated in the HPV16/18-positive cell lines HeLa, SiHa and CaSki, and the mRNA and protein expression were detected. In contrast, the STK31 gene exhibited hypermethylation and silenced expression in the HPV-negative CC cells C33A and HT-3. Compared with the primary HPV-negative CC cell lines, the STK31 methylation was downregulated, and STK31 expression was induced in the HPV16E7/E67 transfected cells. The methylation statuses and expressions of STK31 were verified in the cervical tumor samples at different stages. Additionally, chemotherapy treatment may influence STK31 expression by regulating its methylation status. Conclusions STK31 may be a novel cellular target gene for the HPV16 oncogeneE7. The HPV16 oncogene E7 may affect STK31 expression through a methylation-mediated mechanism. The aberrant methylation of the STK31 promoter/exon 1 region may be a precursor of human cervical carcinogenesis and a potential DNA aberrant methylation biomarker of conditions ranging from precancerous disease to invasive cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12985-016-0515-5) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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