miR-22 and miR-214 targeting BCL9L inhibit proliferation, metastasis, and epithelial-mesenchymal transition by down-regulating Wnt signaling in colon cancer

FASEB J. 2019 Apr;33(4):5411-5424. doi: 10.1096/fj.201801798RR. Epub 2019 Jan 30.


The epithelial-mesenchymal transition (EMT) is crucial for cancer progression. Evidence has shown that miR-22 and miR-214 play a key role in colon cancer progression; however, the underlying mechanism remains to be known. The effects of miR-22 and miR-214 on EMT are contradictory in different cancers, and whether miR-22 and miR-214 are involved in the colon cancer EMT process needs to be elucidated. In this study, we evaluated the exact role and the regulation mechanism of miR-22 and miR-214 in colon cancer. After transfection with miR-22 expression vector, the cell proliferation and migration capacity of HCT116 and RKO cells were significantly suppressed. Also, E-cadherin was increased and vimentin was decreased by miR-22 overexpression. Similar effects were also observed after miR-214 expression vector transfection. Dual-luciferase reporter confirmed that BCL9L is the target gene of both miR-22 and miR-214. Silencing of BCL9L inhibits cell proliferation and migration, and the expression of E-cadherin and vimentin was also altered by BCL9L knockdown, which was consistent with miR-22 or miR-214 transfection. Furthermore, miR-22 and miR-214 inhibited tumor growth in nude mice. Moreover, although the association between BCL9L's lower expression and longer survival time was statistically nonsignificant, a trend existed; further studies in a larger cohort are needed. Collectively, these data suggest that miR-22 and miR-214 inhibit cell proliferation, migration, and EMT of colon cancer, most likely by targeting BCL9L.-Sun, R., Liu, Z., Han, L., Yang, Y., Wu, F., Jiang, Q., Zhang, H., Ma, R., Miao, J., He, K., Wang, X., Zhou, D., Huang, C. miR-22 and miR-214 targeting BCL9L inhibit proliferation, metastasis, and epithelial-mesenchymal transition by down-regulating Wnt signliang in colon cancer.

Keywords: BCL9-2; EMT; carcinoma of colon; microRNA-214; microRNA-22.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cadherins / genetics
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • DNA-Binding Proteins / genetics*
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • HCT116 Cells
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology
  • Transcription Factors / genetics*
  • Vimentin / genetics
  • Wnt Signaling Pathway / genetics*


  • BCL9L protein, human
  • Cadherins
  • DNA-Binding Proteins
  • MIRN214 microRNA, human
  • MIRN22 microRNA, human
  • MicroRNAs
  • Transcription Factors
  • Vimentin