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Peer-reviewedCC BYAdvanced science (Weinheim, Baden-Wurttemberg, Germany)

MZF1 Inhibits TGFβ-1/SMAD Signaling by Transcriptionally Activating SnoN to Augment Tumorigenic Potential in Colon Cancer.

  • Siqi Sheng1
  • Mengxi Huang1
  • Yiting Wang1
  • Hongyu Wang2
  • Haimei Feng2
  • Xiaoming Bai2
  • Jie Chen1
  • Ke Xu1
  • Xiaoyuan Chu1
  • Zengjie Lei1,2,3,4,5
5 affiliations
  1. 1Department of Medical Oncology, Medical School, Affiliated Jinling Hospital, Nanjing University, Nanjing, Jiangsu Province, China.
  2. 2Department of Medical Oncology, Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
  3. 3Department of Medical Oncology, Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
  4. 4Department of Medical Oncology, The First School of Clinical Medicine, Jinling Hospital, Southern Medical University, Nanjing, Jiangsu Province, China.
  5. 5Department of Oncology, School of Medicine, Affiliated Jinling Hospital, Southeast University, Nanjing, China.
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Abstract

Colon cancer progression is associated with transcriptional and signaling abnormalities. MZF1, linked to leukemogenesis, has an unclear role in colon cancer. This study examined its function in colon tumorigenesis and signaling-targeted therapies. Multi-omics (RNA-seq, CUT&Tag) identified MZF1 targets, validated in vitro/in vivo using xenografts and epithelial-specific MZF1 knockout mice. Virtual screening found MZF1 inhibitors. MZF1 activated SnoN transcription, suppressing TGF-β/SMAD signaling. Overexpression enhanced proliferation and colony formation; knockdown reversed these. In vivo, MZF1-overexpressing xenografts grew faster with more Ki67+ cells, while MZF1-/- mice had reduced tumor burden. Organoids from MZF1-/- mice grew poorly. 10Panx Acetate, an MZF1 inhibitor, disrupted MZF1-SnoN interaction, inhibiting cell and xenograft growth. Our results indicate MZF1 as a key colon cancer regulator via SnoN-mediated TGF-β pathway suppression and suggest 10Panx Acetate for precision therapy. MZF1/SnoN co-expression may predict aggressive disease.

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Cite

BibTeXRIS
BibTeX
@article{sheng2026mzf1,
  title = {{MZF1 Inhibits TGFβ-1/SMAD Signaling by Transcriptionally Activating SnoN to Augment Tumorigenic Potential in Colon Cancer.}},
  author = {Siqi Sheng and Mengxi Huang and Yiting Wang and Hongyu Wang and Haimei Feng and Xiaoming Bai and Jie Chen and Ke Xu and Xiaoyuan Chu and Zengjie Lei},
  journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
  year = {2026},
  month = oct,
  doi = {10.1002/advs.77277},
  url = {https://europepmc.org/article/MED/42902510},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - MZF1 Inhibits TGFβ-1/SMAD Signaling by Transcriptionally Activating SnoN to Augment Tumorigenic Potential in Colon Cancer.
AU  - Siqi Sheng
AU  - Mengxi Huang
AU  - Yiting Wang
AU  - Hongyu Wang
AU  - Haimei Feng
AU  - Xiaoming Bai
AU  - Jie Chen
AU  - Ke Xu
AU  - Xiaoyuan Chu
AU  - Zengjie Lei
PY  - 2026
DA  - 2026/10/20
JO  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO  - 10.1002/advs.77277
UR  - https://europepmc.org/article/MED/42902510
AB  - Colon cancer progression is associated with transcriptional and signaling abnormalities. MZF1, linked to leukemogenesis, has an unclear role in colon cancer. This study examined its function in colon tumorigenesis and signaling-targeted therapies. Multi-omics (RNA-seq, CUT&Tag) identified MZF1 targets, validated in vitro/in vivo using xenografts and epithelial-specific MZF1 knockout mice. Virtual screening found MZF1 inhibitors. MZF1 activated SnoN transcription, suppressing TGF-β/SMAD signaling. Overexpression enhanced proliferation and colony formation; knockdown reversed these. In vivo, MZF1-overexpressing xenografts grew faster with more Ki67+ cells, while MZF1-/- mice had reduced tumor burden. Organoids from MZF1-/- mice grew poorly. 10Panx Acetate, an MZF1 inhibitor, disrupted MZF1-SnoN interaction, inhibiting cell and xenograft growth. Our results indicate MZF1 as a key colon cancer regulator via SnoN-mediated TGF-β pathway suppression and suggest 10Panx Acetate for precision therapy. MZF1/SnoN co-expression may predict aggressive disease.
SN  - 2198-3844
ER  -