Abstract：
Mantle cell lymphoma (MCL) is an incurable and aggressive subtype of non-Hodgkin B-cell lymphoma. Increased lipid uptake, storage, and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth. However, no data has been explored for the roles of lipid metabolism reprogramming in MCL. Here, we identified aberrant lipid metabolism reprogramming and PRMT5 as a key regulator of cholesterol and fatty acid metabolism reprogramming in MCL patients. High PRMT5 expression predicts adverse outcome prognosis in 105 patients with MCL and GEO database (GSE93291). PRMT5 deficiency resulted in proliferation defects and cell death by CRISPR/Cas9 editing. Moreover, PRMT5 inhibitors including SH3765 and EPZ015666 worked through blocking SREBP1/2 and FASN expression in MCL. Furthermore, PRMT5 was significantly associated with MYC expression in 105 MCL samples and the GEO database (GSE93291). CRISPR MYC knockout indicated PRMT5 can promote MCL outgrowth by inducing SREBP1/2 and FASN expression through the MYC pathway.
摘要：
套细胞淋巴瘤（MCL）是非霍奇金B细胞淋巴瘤的一种无法治愈的侵袭性亚型。脂质摄取增加，storage,和脂肪生成发生在多种癌症中，并有助于肿瘤的快速生长。然而,目前还没有研究脂质代谢重编程在MCL中的作用的数据.这里,在MCL患者中,我们发现异常脂质代谢重编程和PRMT5是胆固醇和脂肪酸代谢重编程的关键调节因子.高PRMT5表达预测105例MCL和GEO数据库（GSE93291）患者的不良预后。PRMT5缺乏通过CRISPR/Cas9编辑导致增殖缺陷和细胞死亡。此外，包括SH3765和EPZ015666的PRMT5抑制剂通过阻断MCL中的SREBP1/2和FASN表达起作用。此外，在105个MCL样品和GEO数据库(GSE93291)中,PRMT5与MYC表达显著相关。CRISPRMYC敲除表明PRMT5可通过MYC途径诱导SREBP1/2和FASN表达促进MCL长出。
