Histone methyltransferase SETD2: An epigenetic driver in clear cell renal cell carcinoma

Mengxue Yu; Kaiyu Qian; Gang Wang; Yu Xiao; Yuan Zhu; Lingao Ju

doi:10.3389/fonc.2023.1114461

Histone methyltransferase SETD2: An epigenetic driver in clear cell renal cell carcinoma

Front Oncol. 2023 Mar 21:13:1114461. doi: 10.3389/fonc.2023.1114461. eCollection 2023.

Authors

Mengxue Yu¹, Kaiyu Qian², Gang Wang^{1

3}, Yu Xiao^{3

4}, Yuan Zhu³, Lingao Ju^{1

5}

Affiliations

¹ Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.
² Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
³ Human Genetic Resources Preservation Center of Hubei Province, Wuhan, China.
⁴ Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, China.
⁵ Medical Research Institute, Wuhan University, Wuhan, China.

Abstract

SET domain-containing 2 (SETD2) is a lysine methyltransferase that catalyzes histone H3 lysine36 trimethylation (H3K36me3) and has been revealed to play important roles in the regulation of transcriptional elongation, RNA splicing, and DNA damage repair. SETD2 mutations have been documented in several cancers, including clear cell renal cell carcinoma (ccRCC). SETD2 deficiency is associated with cancer occurrence and progression by regulating autophagy flux, general metabolic activity, and replication fork speed. Therefore, SETD2 is considered a potential epigenetic therapeutic target and is the subject of ongoing research on cancer-related diagnosis and treatment. This review presents an overview of the molecular functions of SETD2 in H3K36me3 regulation and its relationship with ccRCC, providing a theoretical basis for subsequent antitumor therapy based on SETD2 or H3K36me3 targets.

Keywords: H3K36me3; SETD2; clear cell renal cell carcinoma (ccRCC); epigenetic regulation; mutation.

Publication types

Review

Grants and funding

This study was supported by the National Natural Science Foundation of China (31900902), Hubei Province health and family planning scientific research project (WJ2023M063), and Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2020-PT320-004).