The inhibition of miR-126 in cell migration and invasion of cervical cancer through regulating ZEB1

Hereditas. 2019 Apr 9;156:11. doi: 10.1186/s41065-019-0087-7. eCollection 2019.

Abstract

Background: Cervical cancer is a malignancy that's common in female with high incidence and mortality worldwide. MicroRNAs (miRNAs) act a pivotal part in human cancer development. Our aim was to investigate the effect of miR-126 on cervical cancer and its underlying molecular mechanism.

Results: Firstly, RT-qPCR assay revealed that the expression of miR-126 was significantly downregulated in cervical cancer tissues and cell lines, compared with that in normal adjacent tissues and normal cervical epithelial cell line (Ect1/E6E7), respectively. Then, ZEB1 was verified as a target of miR-126 by using luciferase reporter assay. Inversely, the expression of ZEB1 was markedly upregulated in tumor tissues, and its mRNA level was negatively regulated by miR-126 expression in SiHa and Hela cells. Moreover, the capability of cell proliferation, migration and invasion was analyzed by CCK-8, wound healing assay and transwell assay, respectively. The results demonstrated that overexpression of miR-126 inhibited SiHa and Hela cell proliferation, migration and invasion, while ZEB1 abolished the inhibition induced by miR-126. Additionally, miR-126 suppressed MMP2 and MMP9 in mRNA and protein levels, as well as inhibited the protein expression of p-JAK2 and p-STAT3 in both SiHa and Hela cells, while ZEB1 rescued miR-126-induced suppression.

Conclusion: miR-126 functions as a tumor suppressor in cervical cancer cells in vitro, which inhibits the proliferation, migration and invasion by suppressing MMP2, MMP9 expression and inactivating JAK2/STAT3 signaling pathway through targeting ZEB1, suggesting that miR-126 might be a novel potential target for the diagnosis and treatment of patients with cervical cancer.

Keywords: Cervical cancer; Invasion; MiR-126; Migration; Proliferation; ZEB1.

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Janus Kinase 2 / metabolism
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • RNA Interference*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • Zinc Finger E-box-Binding Homeobox 1 / genetics*

Substances

  • 3' Untranslated Regions
  • MIRN126 microRNA, human
  • MicroRNAs
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • JAK2 protein, human
  • Janus Kinase 2
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9