Characterizing methylation regulated miRNA in carcinoma of the human uterine cervix

Varghese, Vinay Koshy and Shukla, Vaibhav and Jishnu, Padacherri Vethil and Kabekkodu, Shama Prasada and Pandey, Deeksha and Sharan, Krishna and Kapaettu, Satyamoorthy (2019) Characterizing methylation regulated miRNA in carcinoma of the human uterine cervix. Life Sciences, 232. pp. 1-9. ISSN 0024-3205

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Gene regulatory mechanisms determine the multistep carcinogenesis process. Two aspects of epigenetics are microRNA (miRNAs) and DNA methylation that regulate distinct biological mechanisms such as metastasis,apoptosis cell proliferation and induction of senescence. Although critical, the interplay between these two epigenetic mechanisms is yet to be completely understood, particularly in cervical cancer. To study the DNA methylation regulation of miRNAs and its potential role in cervical cancer, we investigated the differential methylation pattern of two candidate miRNAs (miR-375 and miR-196a-1) during cervical cancer progression against normal cervical epithelium (NCE) by bisulfite DNA sequencing. miR-375 and miR-196a-1 were hypermethylated in Squamous Cell Carcinoma (SCC) against NCE and Cervical Intra-Epithelial Neoplasia (CIN)(p < 0.05). Treatment with demethylating agent reactivated the miR-375 and miR-196a-1 expression in SiHa,HeLa and CaSki cells. In vitro artificial methylation by M.SssI followed by dual luciferase assay confirmed miR-375 and miR-196a-1 as methylation regulated miRNAs (P < 0.05). miR-375 and miR-196a-1 expression levels were negatively correlated with methylation levels in clinical specimens. We further identified Replication Factor C Subunit 3 (RFC3) and High Mobility Group AT-Hook 1 (HMGA1) as targets of miR-375 and miR-196a-1 respectively by dual luciferase reporter assay. Our analysis indicates that miR-375 and miR-196a-1 are DNA methylation regulated miRNAs whose deregulation may facilitate pathophysiology of cervical cancer

Item Type: Article
Uncontrolled Keywords: microRNA; DNA methylation; Cervical cancer; miR-375; miR-196a-1
Subjects: Life Sciences > MLSC Manipal
Medicine > KMC Manipal > Obstetrics & Gynaecology
Medicine > KMC Manipal > Radiotherapy and Oncology
Depositing User: KMC Library
Date Deposited: 13 Sep 2019 06:00
Last Modified: 13 Sep 2019 06:00

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