1. Academic Validation
  2. SMYD2 aggravates gastrointestinal stromal tumor via upregulation of EZH2 and downregulation of TET1

SMYD2 aggravates gastrointestinal stromal tumor via upregulation of EZH2 and downregulation of TET1

  • Cell Death Discov. 2022 Jun 6;8(1):274. doi: 10.1038/s41420-022-01038-w.
Yong Ji  # 1 Xiaofeng Xu  # 2 Cong Long 2 Jianjiang Wang 3 Li Ding 2 Zhizhong Zheng 2 Huiping Wu 4 Liu Yang 2 Lan Tao 5 Feng Gao 6
Affiliations

Affiliations

  • 1 Department of General Gastrointestinal Surgery, Jingjiang People's Hospital, 214500, Jingjiang, P.R. China.
  • 2 Department of Clinical Laboratory, Jingjiang People's Hospital, 214500, Jingjiang, P.R. China.
  • 3 Department of General Surgery, Jingjiang People's Hospital, 214500, Jingjiang, P.R. China.
  • 4 Department of Science and Education, Jingjiang People's Hospital, 214500, Jingjiang, P.R. China.
  • 5 Central Laboratory, Jingjiang People's Hospital, 214500, Jingjiang, P.R. China.
  • 6 Department of General Surgery, Jingjiang People's Hospital, 214500, Jingjiang, P.R. China. 592412678@qq.com.
  • # Contributed equally.
Abstract

SMYD2, as an oncogene, has been involved in multiple types of Cancer, but the potential role of SMYD2 in gastrointestinal stromal tumors (GIST) remains enigmatic and requires further investigation. Hence, this study was conducted with the main objective of analyzing the effect of SMYD2 on GIST. GIST and adjacent normal tissues were collected from 46 patients with GIST where the expression of EZH2, SMYD2, and TET1 was determined, followed by the analysis of their interactions. The functional role of SMYD2 in cell biological functions was determined using a loss-of-function assay in GIST-T1 cells. Nude mouse xenograft experiments were performed to verify the role of the SMYD2/EZH2/TET1 axis in GIST in vivo. EZH2 was upregulated in GIST tissues and cell lines, which was positively correlated with SMYD2 expression and inversely correlated with TET1 expression in GIST tissues. EZH2 silencing due to SMYD2 inhibition reduced GIST-T1 cell proliferation and accelerated cell senescence. EZH2 repressed TET1 expression by promoting H3K27me3 methylation in the TET1 promoter region. TET1 inhibition reversed the effect of EZH2 silencing on the biological functions of GIST-T1 cells. In vivo data further revealed the promoting effect of SMYD2 on the progression of GIST by regulating the EZH2/TET1 axis. Overall, this study demonstrates that SMYD2 can increase EZH2 expression while suppressing TET1 expression, thus accelerating GIST, and creating new treatment opportunities for GIST.

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