The SH3BGR/STAT3 Pathway Regulates Cell Migration and Angiogenesis Induced by a Gammaherpesvirus MicroRNA
Year: 2016
Type: article
Abstract: Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is a gammaherpesvirus etiologically associated with KS, a highly disseminated angiogenic tumor of hyperproliferative spindle endothelial cells. KSHV encodes 25 mature microRNAs but their roles in KSHV-induced tumor dissemination and angiogenesis remain unknown. Here, we investigated KSHV-encoded miR-K12-6-3p (miR-K6-3p) promotion of endothelial cell migration and angiogenesis, which are the underlying mechanisms of tumor dissemination and angiogenesis. We found that ectopic expression of miR-K6-3p promoted endothelial cell migration and angiogenesis. Mass spectrometry, bioinformatics and luciferase reporter analyses revealed that miR-K6-3p directly targeted sequence in the 3' untranslated region (UTR) of SH3 domain binding glutamate-rich protein (SH3BGR). Overexpression of SH3BGR reversed miR-K6-3p induction of cell migration and angiogenesis. Mechanistically, miR-K6-3p downregulated SH3BGR, hence relieved STAT3 from SH3BGR direct binding and inhibition, which was required for miR-K6-3p maximum activation of STAT3 and induction of cell migration and angiogenesis. Finally, deletion of miR-K6 from the KSHV genome abrogated its effect on the SH3BGR/STAT3 pathway, and KSHV-induced migration and angiogenesis. Our results illustrated that, by inhibiting SH3BGR, miR-K6-3p enhances cell migration and angiogenesis by activating the STAT3 pathway, and thus contributes to the dissemination and angiogenesis of KSHV-induced malignancies.
Source: PLoS Pathogens
Authors: Wan Li, Qin Yan, Xiangya Ding, Chenyou Shen, Minmin Hu, Ying Zhu, Di Qin, Hongmei Lu, Brian J. Krueger, Rolf Renne, Shou-Jiang Gao, Chun Lu
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,043
Awards: HIV-1 Nef蛋白促进KSHV K1诱导血管和肿瘤形成：信号通路与miRNAs的作用, Targeting KSHV malignancies and persistent infection, G1988149734, HISTONE MODIFIERS IN ORAL KSHV INFECTION AND MALIGNANCIES, HIV-1 Tat蛋白促进KSHV vIL-6诱导血管生成和肿瘤形成及其分子机制, KSHV Persistence and Pathogenesis, G4779355749, Studying the role of KSHV-encoded miRNAs, G574196841, KSHVmediated regulation of proline metabolism, Mechanism of KSHV-induced angiogenesis, G8151656049, G8711098362, KSHV microRNAs in cellular transformation and tumorigenesis, Regulation of KSHV replication by N6-methyladenosine (m6A)
OpenAlex ID: W2343051666