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  2. MicroRNA-1205 promotes breast cancer cell metastasis by regulating epithelial-to-mesenchymal transition via targeting of CDK3

MicroRNA-1205 promotes breast cancer cell metastasis by regulating epithelial-to-mesenchymal transition via targeting of CDK3

  • Cell Signal. 2024 Jun 17:121:111264. doi: 10.1016/j.cellsig.2024.111264.
Wenjun Guo 1 Wulei Hou 1 Qin Xiang 1 Cheng Chen 2 Heng Yang 2 Shuaihu Li 1 Linhui Ye 1 Tian Xiao 1 Lizhi Zhu 3 Yongdong Zou 4 Duo Zheng 5
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong 518055, PR China.
  • 2 Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong 518055, PR China; Department of Pharmacy, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital (Shenzhen Institute of Translational Medicine), Shenzhen, Guangdong 518055, PR China.
  • 3 Department of Pharmacy, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital (Shenzhen Institute of Translational Medicine), Shenzhen, Guangdong 518055, PR China.
  • 4 Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong 518055, PR China. Electronic address: zouyd@szu.edu.cn.
  • 5 Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong 518055, PR China. Electronic address: dzheng@szu.edu.cn.
Abstract

Metastasis poses a huge obstacle to the survival of breast Cancer patients. The MicroRNA miR-1205 acts as a tumor suppressor in various cancers, but its roles in breast Cancer and metastasis remain unclear. To elucidate its function in breast Cancer progression, we analyzed miR-1205 expression in human tumor samples and carried out a series of functional studies in in vitro and in vivo. miR-1205 was expressed more highly in metastatic breast tumor samples than in non-metastatic samples and was associated with lymph node metastasis, clinical stage, and poor prognosis. Moreover, miR-1205 promoted breast Cancer cell invasiveness in vitro and metastasis in mice by directly targeting CDK3 and reducing CDK3 protein levels. We also showed that CDK3 interacts with Snail protein, inducing Snail degradation via the ubiquitin-proteasome system and potentially affecting epithelial-to-mesenchymal transition. Furthermore, analysis of clinical tissue samples indicated that CDK3 and miR-1205 levels were inversely correlated in lymph node metastasis-positive primary tumors. This study demonstrated the pro-metastatic role of miR-1205 in breast Cancer, mediated via a novel miR-1205/CDK3/Snail axis. Moreover, we identified miR-1205 and CDK3 as potential markers of invasion and progression in breast Cancer.

Keywords

Breast cancer; CDK3; Metastasis; Snail; miR-1205.

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