2. Academic Validation
  3. ZWINT down-regulated by miR-495-3p inhibited lung metastasis of breast cancer by blocking p38 MAPK signaling pathway activation

ZWINT down-regulated by miR-495-3p inhibited lung metastasis of breast cancer by blocking p38 MAPK signaling pathway activation

  • Hum Cell. 2025 Oct 4;38(6):170. doi: 10.1007/s13577-025-01301-z.
Ming-Tao Shao 1 2,  Wei-Wen Li 3,  Yong Li 3,  Ping Chen 4,  Shuai-Shuai Yu 5,  Wen-Jie Lu 6,  Chun-Mei Chen 3,  Yan Dong 3,  Yi-Wen Zhang 3,  Qun-Chen Zhang 3
Affiliations

Affiliations

  • 1 Department of Breast Medical Center, Jiangmen Central Hospital, Jiangmen, Guangdong, China. sdbxsmt@163.com.
  • 2 Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China. sdbxsmt@163.com.
  • 3 Department of Breast Medical Center, Jiangmen Central Hospital, Jiangmen, Guangdong, China.
  • 4 Department of Pathology, Jiangmen Central Hospital, Jiangmen, Guangdong, China.
  • 5 Department of Clinical Laboratory, Jiangmen Central Hospital, Jiangmen, Guangdong, China.
  • 6 Department of Medical Research Center, Jiangmen Central Hospital, Jiangmen, Guangdong, China.
PMID: 41046283 DOI: 10.1007/s13577-025-01301-z
Abstract

Breast Cancer metastasis is the primary cause of patient mortality, yet effective therapeutic targets remain limited. Building on our prior identification of ZWINT as a prognostic marker linked to metastasis, this study defines its critical functional role and regulatory mechanism. Multi-omics analysis revealed a strong association between ZWINT expression and metastatic processes across breast Cancer subtypes. Functionally, ZWINT knockdown significantly inhibited breast Cancer cell migration and invasion in vitro and dramatically reduced lung metastasis in vivo. Mechanistically, we discovered that miR-495-3p directly targets and suppresses ZWINT expression, and this miR-495-3p/ZWINT axis acts through inhibiting p38 MAPK pathway activation to suppress metastatic progression in vitro. Our findings demonstrate that ZWINT drives breast Cancer metastasis and is negatively regulated by miR-495-3p. The newly identified miR-495-3p/ZWINT/p38 MAPK axis may provide a promising therapeutic target for suppressing breast Cancer progression.

Keywords

Breast cancer; Lung metastasis; MiR-495-3p; P38 MAPK pathway; ZWINT.

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