期刊
NUCLEIC ACIDS RESEARCH
卷 43, 期 19, 页码 9362-9378出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkv988
关键词
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资金
- National Natural Science Foundation of China [81361120387, 81371824, 81171552, 31270199, 81401662, 81571984]
- NIH [R01CA177377, R01CA132637]
- Ph.D. Programs Foundation of Ministry of Education of China [20123234110006]
- Natural Science Youth Foundation of Jiangsu Province [BK20140908]
- Quzhou Science and Technology Bureau [2013Y020]
Co-infection with HIV-1 and Kaposi's sarcoma-associated herpesvirus (KSHV) is the cause of aggressive AIDS-related Kaposi's sarcoma (AIDS-KS) characterized by abnormal angiogenesis. The impact of HIV-1 and KSHV interaction on the pathogenesis and extensive angiogenesis of AIDS-KS remains unclear. Here, we explored the synergistic effect of HIV-1 Tat and KSHV oncogene Orf-K1 on angiogenesis. Our results showed that soluble Tat or ectopic expression of Tat enhanced K1-induced cell proliferation, microtubule formation and angiogenesis in chorioallantoic membrane and nude mice models. Mechanistic studies revealed that Tat promoted K1-induced angiogenesis by enhancing NF-kappa B signaling. Mechanistically, we showed that Tat synergized with K1 to induce the expression of miR-891a-5p, which directly targeted I alpha B alpha 3' untranslated region, leading to NF-kappa B activation. Consequently, inhibition of miR-891a-5p increased I alpha B alpha level, prevented nuclear translocation of NF-kappa B p65 and ultimately suppressed the synergistic effect of Tat-and K1-induced angiogenesis. Our results illustrate that, by targeting I alpha B alpha to activate the NF-kappa B pathway, miR-891a-5p mediates Tat and K1 synergistic induction of angiogenesis. Therefore, the miR-891a-5p/NF-kappa B pathway is important in the pathogenesis of AIDS-KS, which could be an attractive therapeutic target for AIDS-KS.
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