Identification of the H3K36me3 reader LEDGF/p75 in the pancancer landscape and functional exploration in clear cell renal cell carcinoma

Yuwei Zhang; Wei Guo; Yangkun Feng; Longfei Yang; Hao Lin; Pengcheng Zhou; Kejie Zhao; Lin Jiang; Bing Yao; Ninghan Feng

Computational and Structural Biotechnology Journal (Jan 2023)

Identification of the H3K36me3 reader LEDGF/p75 in the pancancer landscape and functional exploration in clear cell renal cell carcinoma

Yuwei Zhang,
Wei Guo,
Yangkun Feng,
Longfei Yang,
Hao Lin,
Pengcheng Zhou,
Kejie Zhao,
Lin Jiang,
Bing Yao,
Ninghan Feng

Affiliations

Yuwei Zhang: Nantong University Medical School, Nantong, China; Department of Urology, Jiangnan University Medical Center, Wuxi, China
Wei Guo: Department of Urology, Jiangnan University Medical Center, Wuxi, China
Yangkun Feng: Nantong University Medical School, Nantong, China
Longfei Yang: Nantong University Medical School, Nantong, China; Department of Urology, Jiangnan University Medical Center, Wuxi, China
Hao Lin: Department of Urology, Jiangnan University Medical Center, Wuxi, China
Pengcheng Zhou: Department of Medical Genetics, Nanjing Medical University, Nanjing, China
Kejie Zhao: Department of Medical Genetics, Nanjing Medical University, Nanjing, China
Lin Jiang: Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Correspondence to: Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
Bing Yao: Department of Medical Genetics, Nanjing Medical University, Nanjing, China; Correspondence to: Department of Medical Genetics, Nanjing Medical University, 101 Longmian Road, Nanjing 211166, China.
Ninghan Feng: Nantong University Medical School, Nantong, China; Department of Urology, Jiangnan University Medical Center, Wuxi, China; Wuxi School of Medicine, Jiangnan University, Wuxi, China; Correspondence to: Nantong University Medical School, 9 Qiangyuan Road, Nantong 226019, China.

Journal volume & issue: Vol. 21
pp. 4134 – 4148

Abstract

Read online

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.

Published in Computational and Structural Biotechnology Journal

ISSN: 2001-0370 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Technology: Chemical technology: Biotechnology
Website: https://www.journals.elsevier.com/computational-and-structural-biotechnology-journal

About the journal

Abstract

Keywords