KSHV MicroRNAs Repress Tropomyosin 1 and Increase Anchorage-Independent Growth and Endothelial Tube Formation
作者： Philippe Kieffer-Kwon , Christine Happel , Thomas S. Uldrick , Dhivya Ramalingam , Joseph M. Ziegelbauer
DOI: 10.1371/JOURNAL.PONE.0135560
关键词: Kaposi's sarcoma-associated herpesvirus 、 Tropomyosin 、 Cell biology 、 Regulation of gene expression 、 Three prime untranslated region 、 Molecular biology 、 Vascular endothelial growth factor A 、 Anoikis 、 Tube formation 、 Gene isoform 、 Biology 、 General Biochemistry, Genetics and Molecular Biology 、 General Agricultural and Biological Sciences 、 General Medicine
摘要: Kaposi’s sarcoma (KS) is characterized by highly vascularized spindle-cell tumors induced after infection of endothelial cells sarcoma-associated herpesvirus (KSHV). In KS tumors, KSHV expresses only a few latent proteins together with 12 pre-microRNAs. Previous microarray and proteomic studies predicted that multiple splice variants the tumor suppressor protein tropomyosin 1 (TPM1) were targets microRNAs. Here we show at least two microRNAs KSHV, miR-K2 miR-K5, repress levels specific isoforms TPM1. We identified functional miR-K5 binding site in 3’ untranslated region (UTR) one TPM1 isoform. Furthermore, inhibition or loss restores expression KSHV-infected cells. also repressed clinical samples compared to uninfected samples. Functionally, increases viability unanchored human umbilical vein (HUVEC) inhibiting anoikis (apoptosis cell detachment), enhances tube formation HUVECs, VEGFA expression. Taken together, may facilitate pathogenesis.
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