Zhang Yuwei, Guo Wei, Feng Yangkun, Yang Longfei, Lin Hao, Zhou Pengcheng, Zhao Kejie, Jiang Lin, Yao Bing, Feng Ninghan
Nantong University Medical School, Nantong, China.
Department of Urology, Jiangnan University Medical Center, Wuxi, China.
Comput Struct Biotechnol J. 2023 Aug 26;21:4134-4148. doi: 10.1016/j.csbj.2023.08.023. eCollection 2023.
Lens epithelium-derived growth factor (LEDGF/p75) is a reader of epigenetic marks and a potential target for therapeutic intervention. Its involvement in human immunodeficiency virus (HIV) integration and the development of leukemia driven by MLL (also known as KMT2A) gene fusion make it an attractive candidate for drug development. However, exploration of LEDGF/p75 as an epigenetic reader of H3K36me3 in tumors is limited. Here, for the first time, we analyze the role of LEDGF/p75 in multiple cancers via multiple online databases and in vitro experiments. We used pancancer bulk sequencing data and online tools to analyze correlations of LEDGF/p75 with prognosis, genomic instability, DNA damage repair, prognostic alternative splicing, protein interactions, and tumor immunity. In summary, the present study identified that LEDGF/p75 may serve as a prognostic predictor for tumors such as adrenocortical carcinoma, kidney chromophobe, liver hepatocellular carcinoma, pancreatic adenocarcinoma, skin cutaneous melanoma, and clear cell renal cell carcinoma (ccRCC). In addition, in vitro experiments and gene microarray sequencing were performed to explore the function of LEDGF/p75 in ccRCC, providing new insights into the pathogenesis of the nonmutated SETD2 ccRCC subtype.
晶状体上皮衍生生长因子（LEDGF/p75）是一种表观遗传标记的读取蛋白，也是治疗干预的潜在靶点。它参与人类免疫缺陷病毒（HIV）整合以及由混合系白血病（MLL，也称为KMT2A）基因融合驱动的白血病发展，这使其成为药物开发的一个有吸引力的候选对象。然而，在肿瘤中探索LEDGF/p75作为H3K36me3的表观遗传读取蛋白的研究还很有限。在此，我们首次通过多个在线数据库和体外实验分析了LEDGF/p75在多种癌症中的作用。我们使用泛癌批量测序数据和在线工具分析了LEDGF/p75与预后、基因组不稳定性、DNA损伤修复、预后选择性剪接、蛋白质相互作用和肿瘤免疫的相关性。总之，本研究确定LEDGF/p75可能作为肾上腺皮质癌、肾嫌色细胞癌、肝细胞肝癌、胰腺腺癌、皮肤黑色素瘤和透明细胞肾细胞癌（ccRCC）等肿瘤的预后预测指标。此外，还进行了体外实验和基因微阵列测序以探索LEDGF/p75在ccRCC中的功能，为未发生突变的SETD2 ccRCC亚型的发病机制提供了新的见解。
