High-risk HPV infection modulates the promoter hypermethylation of APC, SFRP1 , and PTEN in cervical cancer patients of
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ORIGINAL ARTICLE
High‑risk HPV infection modulates the promoter hypermethylation of APC, SFRP1, and PTEN in cervical cancer patients of North India Lokesh Kumari Kadian1 · Ritu Yadav1 · Smiti Nanda2 · Gulshan Gulshan3 · Shivkant Sharma1 · Chetna Yadav1 Received: 8 May 2020 / Accepted: 29 October 2020 © Springer Nature B.V. 2020
Abstract Persistent infection with oncogenic HPV and downregulation of tumor suppressor genes play an essential role in the development and progression of cervical cancer. The present study aimed to identify the promoter methylation status of APC, SFRP1, and PTEN which are important regulators of Wnt pathway and their association with high-risk HPV infection and gene expression. Methylation Specific PCR (MSP) and quantitative reverse transcription PCR (RT-qPCR) were used to detect methylation status and gene expression levels of APC, SFRP1, and PTEN in cervical cancer biopsies (110) and paired non-cancerous biopsies (28). APC promoter was methylated in 38%, SFRP1 in 95%, and PTEN in 55% of the cervical cancer biopsies. Our data showed a trend of a higher rate of methylation of the gene promoters in cervical cancer biopsies while; they were majorly un-methylated in non-cancerous biopsies. Corresponding to a higher rate of methylation in cancer biopsies, the gene expression levels of APC, SFRP1, and PTEN were reduced in cervical cancer samples in comparison to normal cervix tissues. Further, we observed that 97% cancer biopsies were HPV infected and high-risk type HPV16 and 18 infections were significantly positively associated with APC (p = 0.008 and p = 0.007), SFRP1 (p = 0.003 and p = 0.0067), and PTEN (p = 0.049 and p = 0.008) promoter methylation. APC, SFRP1, and PTEN promoter hyper-methylation is positively associated with high-risk HPV infection and inversely associated with gene expression. Our findings show that high-risk HPV infection promotes methylation of these genes and further promotes their silencing. Keywords Cervical cancer · Promoter hypermethylation · Gene expression · HPV infection Abbreviations IHEC Institutional human ethical committee qRT-PCR Quantitative real-time polymerase chain reaction MSP Methylation specific PCR HPV Human papillomavirus
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05960-z) contains supplementary material, which is available to authorized users. * Ritu Yadav [email protected] 1
Department of Genetics, Maharishi Dayanand University, Rohtak 124001, Haryana, India
2
Departments of Obstetrics and Gynaecology, PGIMS, Rohtak, Haryana, India
3
Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, Maharashtra, India
Introdcution Cancer is the second major cause of death worldwide, killing more people than AIDS, tuberculosis, and malaria altogether [1]. Late-stage diagnosis and lack of appropriate treatment are common reasons for most cancer-related deaths especially in developing countries. In India, cervical cancer is major gynecological cancer
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