Research Paper Advance Articles
Histone methyltransferase SETD2 inhibits tumor growth via suppressing CXCL1-mediated activation of cell cycle in lung adenocarcinoma
- 1 Department of Tumor Biological Treatment, the Third Affiliated Hospital of Soochow University, Changzhou 213003, China
- 2 Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou 213003, China
- 3 Institute of Cell Therapy, Soochow University, Changzhou 213003, China
Received: February 1, 2020 Accepted: August 27, 2020 Published: November 20, 2020https://doi.org/10.18632/aging.104120
How to Cite
Copyright: © Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The histone H3 lysine 36 methyltransferase SET-domain-containing 2 (SETD2) has been reported to be frequently mutated or deleted in many types of human cancer. However, the role of SETD2 in lung adenocarcinoma (LUAD) has not been well documented. In the present study, we found that SETD2 was significantly down-regulated both in LUAD tissues and cell lines. Functionally, the increased expression of SETD2 significantly attenuated the proliferation of cancer cells by affecting the cell cycle, whereas SETD2 deficiency dramatically improved these proliferative abilities of cancer cells. Through conjoint analysis of RNA-seq and ChIP data, we identified a functional target gene of SETD2, CXCL1, and its expression was negatively correlated with that of SETD2. Moreover, SETD2 deletion stimulated cell cycle-related proteins to promote LUAD. Further mechanistic studies demonstrated that histone H3 lysine 36 trimethylation (H3K36me3) catalyzed by SETD2 interacted with the promoter of CXCL1 to regulate its transcription and downstream signaling pathways, contributing to tumorigenesis in vitro and in vivo. Our findings suggested that SETD2 inhibited tumor growth via suppressing CXCL1-mediated activation of cell cycle, indicating that the regulation of H3K36me3 level by targeting SETD2 and/or the administration of downstream CXCL1 might represent a potential therapeutic way for new treatment in LUAD.