Anuradha Garg
Post Graduate Institute of Medical Education & Research (PGIMER), India
Title: APOBEC3G governs cellular oncogenic transformation
Biography
Biography: Anuradha Garg
Abstract
The oncogenic potential of APOBEC3G gene was recently appreciated by its inhibitory influence of APOBEC3G upon miRNA-mediated repression of the gene responsible for hepatic metastasis. The present study employed human PBMCs, as an archetype model to understand the role of APOBEC3G in regulation of gene involved in oncogenesis. Such a study revealed that APOBEC3G transrepresses KLF4 by binding to its mRNA at 3’UTR. This phenomenon was paralleled by the sustained expression of the cellular SP1 that ensured overexpression of genes coding for c-myc, Bmi-1, BCL-2 and MDM2 coupled with downregulation of p53 in PBMCs thereby creating a favorable situation for oncogenic transformation. Additionally, cell cycle regulators like Cyclin D, B and E were found to be upregulated, along with increase in S-phase of the cell cycle. Furthermore, study revealed role of APOBEC3G in tailoring immune response that could help tumor growth through escape of immunosurveillance. This study unambiguously revealed that APOBEC3G has the inherent capacity to upregulate genes coding for STAT3, CCL5, IL-6, IL-4, and NF-κB coupled with downregulation of IL-10, IL-17. Based upon these results, we propose that increased expression of APOBEC3G could have the inherent capacity to ensure alterations of gene expression in such a way that leads to cellular proliferation, hallmark of oncogenesis as well as make the environment conducive for tumor progression and immune escape through its ability to ensure sustained chronic inflammation. This may add a new dimension to understand oncogenesis in general, and the novel role of APOBEC3G in the oncogenic process in particular.