2. Academic Validation
  3. MiR-377-3p suppresses colorectal cancer through negative regulation on Wnt/β-catenin signaling by targeting XIAP and ZEB2

MiR-377-3p suppresses colorectal cancer through negative regulation on Wnt/β-catenin signaling by targeting XIAP and ZEB2

  • Pharmacol Res. 2020 Jun;156:104774. doi: 10.1016/j.phrs.2020.104774.
Lifeng Huang 1,  Zhibo Liu 2,  Jia Hu 3,  Zhen Luo 3,  Cheng Zhang 3,  Lin Wang 4,  Zheng Wang 5
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 2 Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 3 Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 4 Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address: lin_wang@hust.edu.cn.
  • 5 Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address: zhengwang@hust.edu.cn.
PMID: 32220639 DOI: 10.1016/j.phrs.2020.104774
Abstract

Aberrant activation of Wnt/β-catenin signaling is a common event in the development of colorectal Cancer (CRC). It is important to identify new molecules and mechanisms that can negatively regulate Wnt/β-catenin signaling. MicroRNAs are considered as promising candidates for Cancer diagnosis and therapy. In our study, we found that miR-377-3p was significantly decreased in CRC samples compared to the normal mucosa tissues, especially in the patients at stage III/IV. Functional studies showed that overexpression of miR-377-3p suppressed and silence of miR-377-3p enhanced the proliferation, migration and chemoresistance of CRC cells. Molecularly, miR-377-3p inhibited Wnt/β-catenin signaling by directly targeting ZEB2 and XIAP, which were the positive regulators of Wnt/β-catenin signaling. Overexpression of ZEB2/XIAP could counteract the tumor suppressing phenotypes induced by miR-377-3p. Therefore, we uncovered the anti-cancer role and the relevant mechanisms of miR-377-3p in CRC, which might provide novel targets for designing new anti-tumor strategies.

Keywords

Colorectal cancer; MiR-377-3p; XIAP; ZEB2; β-catenin.

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