KSHV-Mediated Regulation of Par3 and SNAIL Contributes to B-Cell Proliferation

Studies have suggested that epithelial–mesenchymal transition (emt) and transformation is an important step in progression to cancer. par3 (partitioning-defective protein) is a crucial factor in regulating epithelial cell polarity. however,the mechanism by which the latency associated nuclear antigen (lana) encoded by kaposi's sarcoma associated herpesvirus (kshv) regulates par3 and emts markers (epithelial-mesenchymal transition) during viral-mediated b-cell oncogenesis has not been fully explored. moreover,several studies have demonstrated a crucial role for emt markers during b-cell malignancies. in this study,we demonstrate that par3 is significantly up-regulated in kshv-infected primary b-cells. further,par3 interacted with lana in kshv positive and lana expressing cells which led to translocation of par3 from the cell periphery to a predominantly nuclear signal. par3 knockdown led to reduced cell proliferation and increased apoptotic induction. levels of snail was elevated,and e-cadherin was reduced in the presence of lana or par3. interestingly,kshv infection in primary b-cells led to enhancement of snail and down-regulation of e-cadherin in a temporal manner. importantly,knockdown of snail,a major emt regulator,in kshv cells resulted in reduced expression of lana,par3,and enhanced e-cadherin. also,snail bound to the promoter region of p21 and can regulate its activity. further a snail inhibitor diminished nf-kb signaling through upregulation of caspase3 in kshv positive cells in vitro. this was also supported by upregulation of snail and par3 in bc-3 transplanted nod-scid mice which has potential as a therapeutic target for kshv-associated b-cell lymphomas. © 2016 jha et al.