RNA结合蛋白hnRNP Q介导卡波氏肉瘤病毒（KSHV）编码的vIRF1诱导内皮细胞迁移侵袭的功能研究

卡波氏肉瘤（KS）是一种艾滋病患者最常伴发的内皮细胞来源的高度侵袭与转移性恶性肿瘤，转移后的KS预后差、死亡率高。KS转移的机制尚不清楚。课题组近来的研究发现，KS的病原体卡波氏肉瘤病毒（KSHV）编码的病毒干扰素调节因子1（vIRF1）通过调控细胞非编码RNA诱导内皮细胞迁移侵袭（PLoS Pathog 2019），但具体分子机制尚未完全阐明。近期预实验的结果提示，vIRF1可能与RNA结合蛋白hnRNP Q结合并抑制其表达，促进内皮细胞迁移侵袭。本项目拟（1）证实vIRF1与hnRNP Q相结合并阐明其抑制hnRNP Q蛋白表达的分子机制；（2）鉴定与hnRNP Q结合的下游关键mRNA及其功能；（3）运用反向遗传互补实验进一步证实hnRNP Q及其下游mRNA参与vIRF1诱导内皮细胞迁移侵袭。本项目致力于阐明KSHV诱导KS恶性转移的发病机制，为转移性KS的诊疗提供潜在的分子靶点。

Kaposi's sarcoma (KS) is an endothelial cells-derived malignant tumor that frequently happens to AIDS patients, which is with high invasion and metastasis, poor prognosis and significant mortality. The mechanism of KS metastasis still need to be clarified. As oncogenic protein, viral interferon regulatory factor 1 (vIRF1), encoded by KSHV as the causative agent of KS, has been shown to promote cell migration and invasion by regulation of non-coding RNA in our previous study, however, its underlying mechanisms remain unknown. Our recent pre-experiment showed that vIRF1 may induce cell migration and invasion by interacting with heterogeneous nuclear ribonucleoprotein Q (hnRNP Q), as well as vIRF1-mediated downregulation of hnRNP Q and its downstream genes. Thus, our expectations are to identify the association between vIRF1 and hnRNP Q, to elucidate the molecular mechanisms of vIRF1-mediated downregulation of hnRNP Q and hnRNP Q regulated critical mRNA-induced cell migration and invasion, and to further confirm that hnRNP Q and the downstream genes participate in vIRF-1-induced cell migration, invasion and tumorigenesis using reverse genetics assay. Our research will contribute to clarify the pathogenesis of KS induced by KSHV and provide potential targets for clinical prevention and therapy of AIDS-KS.