miR-377-3p drives malignancy characteristics via upregulating GSK-3β expression and activating NF-κB pathway in hCRC cells

J Cell Biochem. 2018 Feb;119(2):2124-2134. doi: 10.1002/jcb.26374. Epub 2017 Oct 23.

Abstract

MicroRNA (miRNA) dysregulation has been associated with carcinogenesis in many cancers, including human colorectal cancer (hCRC). However, the effect and mechanism of miR-377-3p on CRC remains elusive. Herein, we first found that miR-377-3p was upregulated in CRC tissues and promoted tumorigenic activity by accelerating the G1 -S phase transition, promoting cell proliferation and epithelial-mesenchymal transition (EMT) while repressing apoptosis in CRC cells. Glycogen synthase kinase-3β (GSK-3β) was a direct target of miR-377-3p, and upregulated by miR-377-3p. Knockdown of GSK-3β partly rescued miR-377-3p-mediated malignancy characteristics. Most importantly, we showed that miR-377-3p promoted carcinogenesis by activating NF-κB pathway. Taken together, our results first reported that miR-377-3p functions as an oncogene and promotes carcinogenesis via upregulating GSK-3β expression and activating NF-κB pathway in hCRC cells.

Keywords: CRC; GSK-3β; NF-κB; miR-377-3p; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics*
  • Gene Expression Regulation, Neoplastic
  • Glycogen Synthase Kinase 3 beta / genetics*
  • HCT116 Cells
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • NF-kappa B / genetics
  • Neoplasm Transplantation
  • Signal Transduction*
  • Up-Regulation*

Substances

  • 3' Untranslated Regions
  • MIRN377 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta