Epigenetic Regulation of miR-92a and TET2 and Their Association in Non-Hodgkin Lymphoma

Esther K Elliott; Lloyd N Hopkins; Robert Hensen; Heidi G Sutherland; Larisa M Haupt; Lyn R Griffiths

doi:10.3389/fgene.2021.768913

Epigenetic Regulation of miR-92a and TET2 and Their Association in Non-Hodgkin Lymphoma

Front Genet. 2021 Nov 26:12:768913. doi: 10.3389/fgene.2021.768913. eCollection 2021.

Authors

Esther K Elliott^{1

2}, Lloyd N Hopkins¹, Robert Hensen², Heidi G Sutherland¹, Larisa M Haupt¹, Lyn R Griffiths¹

Affiliations

¹ Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Queensland University of Technology (QUT), Kelvin Grove, QLD, Australia.
² Icon Cancer Centre, Brisbane, QLD, Australia.

Abstract

MicroRNAs (miRNAs) are well known for their ability to regulate the expression of specific target genes through degradation or inhibition of translation of the target mRNA. In various cancers, miRNAs regulate gene expression by altering the epigenetic status of candidate genes that are implicated in various difficult to treat haematological malignancies such as non-Hodgkin lymphoma by acting as either oncogenes or tumour suppressor genes. Cellular and circulating miRNA biomarkers could also be directly utilised as disease markers for diagnosis and monitoring of non-Hodgkin lymphoma (NHL); however, the role of DNA methylation in miRNA expression regulation in NHL requires further scientific inquiry. In this study, we investigated the methylation levels of CpGs in CpG islands spanning the promoter regions of the miR-17-92 cluster host gene and the TET2 gene and correlated them with the expression levels of TET2 mRNA and miR-92a-3p and miR-92a-5p mature miRNAs in NHL cell lines, tumour samples, and the whole blood gDNA of an NHL case control cohort. Increased expression of both miR-92a-3p and miR-92a-5p and aberrant expression of TET2 was observed in NHL cell lines and tumour tissues, as well as disparate levels of dysfunctional promoter CGI methylation. Both miR-92a and TET2 may play a concerted role in NHL malignancy and disease pathogenesis.

Keywords: Burkitt lymphoma; DNA methylation; diffuse large B-cell lymphoma; epigenetic regulation; mantle cell lymphoma; miR-17∼92; micro-RNA (miRNA/miR).