2. Academic Validation
  3. ZC3H13 mediates N6-methyladenosine modification of SNTB1 to promote epithelial-mesenchymal transition in gastric cancer

ZC3H13 mediates N6-methyladenosine modification of SNTB1 to promote epithelial-mesenchymal transition in gastric cancer

  • Cell Death Dis. 2025 Aug 7;16(1):596. doi: 10.1038/s41419-025-07889-2.
Xiaozhou Xie # 1 2 3,  Yulong Zhao # 1 2 3 4,  Jin Liu # 5 6,  Han Li # 7,  Xingyu Zhu 1 2 3,  Yuan Liu 1 2,  Yaodong Sang 1 2 3,  Kang Xu 1 2 3,  Fengying Du 1 2 3,  Huicheng Ren 8,  Xiaoling Cui 1 2 3,  Baoshan Cai 1 2 3,  Hao Chen 9,  Nanping Wu 4,  Guihua Hou 5,  Changqing Jing 10 11 12,  Wei Chong 13 14 15,  Leping Li 16 17 18,  Liang Shang 19 20 21
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • 2 Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan, China.
  • 3 Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
  • 4 Cell Biology Research Platform, Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China.
  • 5 Research Center for Experimental Nuclear Medicine, School of Basic Medical Sciences, Shandong University, Jinan, China.
  • 6 Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • 7 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
  • 8 Department of Gastrointestinal Surgery, Zibo Central Hospital, Zibo, China.
  • 9 Clinical Research Center of Shandong University, Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China.
  • 10 Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. jingchangqing@sdfmu.edu.cn.
  • 11 Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan, China. jingchangqing@sdfmu.edu.cn.
  • 12 Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China. jingchangqing@sdfmu.edu.cn.
  • 13 Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. chongwei.good@163.com.
  • 14 Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan, China. chongwei.good@163.com.
  • 15 Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China. chongwei.good@163.com.
  • 16 Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. lileping@medmail.com.cn.
  • 17 Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan, China. lileping@medmail.com.cn.
  • 18 Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China. lileping@medmail.com.cn.
  • 19 Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. docshang@163.com.
  • 20 Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan, China. docshang@163.com.
  • 21 Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China. docshang@163.com.
  • # Contributed equally.
PMID: 40774945 DOI: 10.1038/s41419-025-07889-2
Abstract

Gastric Cancer (GC) is one of the highly aggressive human malignant tumors. However, as one of the components of m6A methylation, ZC3H13 has not been reported to regulate the occurrence and development of GC. We determined the expression of ZC3H13 in GC and its correlation with prognosis using the TCGA and ACRG datasets. The effect of ZC3H13 on GC was elucidated through in vivo and in vitro assays. Next, we identified the downstream target of ZC3H13 via MeRIP-seq, and RNA-seq combined with multi-omics analysis, and explored the regulatory mechanism of ZC3H13 in GC using methods such as immunoprecipitation. We found that ZC3H13 is highly expressed in GC tissues and contributes to the poor prognosis of GC patients. ZC3H13 promoted the proliferation, invasion and migration of GC cells in vivo and in vitro, possibly by facilitating the EMT process. In addition, SNTB1 was identified as a downstream target of ZC3H13. ZC3H13-regulated YTHDF1-dependent m6A modification led to post-transcriptional activation of SNTB1 and induce phenotypic changes and EMT activation in GC cells. We determined that ZC3H13 is significantly upregulated in GC and promotes its progression. ZC3H13 mediated YTHDF1-dependent m6A modification of SNTB1 promotes the progression of GC by influencing the EMT process. Our study is the first to report the crucial role of ZC3H13 mediated m6A modification in GC, and we believe that ZC3H13 can serve as a potential therapeutic target for GC.

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