卡波氏肉瘤病毒（KSHV）引起的原发性渗出性淋巴瘤（PEL）是AIDS的重要并发症，其特征为高度恶性和细胞异常增殖，目前无特效治疗方案，患者生存期短。KSHV编码的miRNAs能够促进PEL细胞增殖与存活。近来研究提示KSHV病毒基因组RNA的N6-甲基腺嘌呤（m6A）修饰在其致病过程中具有重要作用。那么，KSHV是否通过调控宿主基因m6A修饰促进PEL细胞增殖与存活？课题组预实验结果表明，m6A修饰因子甲基转移酶3（METTL3）的低表达促进了PEL细胞增殖和存活；部分KSHV miRNAs可靶向抑制METTL3。为此本项目拟：1）证实METTL3对PEL细胞增殖与存活的调控作用；2）鉴定靶向METTL3的KSHV miRNAs以及METTL3下游靶基因；3）研究METTL3在上述过程中调控靶基因的作用机制。本项目致力于阐明PEL的致瘤机理，为PEL临床治疗提供有效的分子靶点。

Primary effusion lymphoma (PEL), caused by Kaposi's sarcoma-associated herpesvirus (KSHV), is an important complication of AIDS and is characterized by high malignancy and abnormal lymphocyte proliferation. There is no standard treatment available for PEL at present. Thus, the median survival of PEL patients is less than 6 months. MicroRNAs (miRNAs) encoded by KSHV exhibit the potential to promote the proliferation and survival of PEL cells. Recent studies have suggested that N6-methyladenine (m6A) modification of viral genome RNA plays an important role in KSHV pathogenesis. However, whether KSHV promotes PEL cells proliferation and survival by regulating m6A modification of host genes remains unclear. The results of our preliminary experiments indicated that the lower expression level of m6A “writer” protein methyltransferase like 3 (METTL3) promoted the proliferation and survival of PEL cells, and partial KSHV miRNAs showed the potential of targeting METTL3. Therefore, the expectations of this project are: 1. to confirm the role of METTL3 in regulating the proliferation and survival of PEL cells; 2. to identify KSHV miRNAs targeting METTL3 and the downstream genes of METTL3; 3. to study the mechanism of METTL3 regulating downstream genes in above process. This project will shed light on the mechanisms of PEL tumorigenesis, and will provide effective molecular targets for its clinical treatment.