MicroRNA-374b inhibits cervical cancer cell proliferation and induces apoptosis through the p38/ERK signaling pathway by binding to JAM-2

J Cell Physiol. 2018 Sep;233(9):7379-7390. doi: 10.1002/jcp.26574. Epub 2018 Mar 25.


Cervical cancer (CC) remains a highly prevalent cancer and mortality globally among women globally. The aim of the present study was to assess the ability of miR-374b to regulate CC cells through JAM-2, whilst exploring whether the underlying mechanism and its relation to the p38/ERK signaling pathway. During the study, microRNA-374b (miR-374b) was observed to have been expressed at a low level among CC tissues. Hence, a series of miR-374b mimics, miR-374b inhibitors, siRNA against JAM-2, SB202190 (an inhibitor for p38), and PD98059 (an inhibitor for ERK) were introduced to treat CC Siha cells and normal cervical Ect1/E6E7 cells. MTT, flow cytometry, scratch test, and transwell assays were applied to determine cell viability, apoptosis, migration, and invasion. The inhibitory role of the p38/ERK signaling pathway was observed in the CC cells treated with miR-374b mimics or siRNA against JAM-2. miR-374b mimic exposure was found to reduce cell viability, migration, and invasion, but induce apoptosis. MiR-374b inhibitor exposure was observed to have induced effects on the CC cells in a contrary manner to those induced by that of the miR-374b mimics. The key findings of the study demonstrated that miR-374b significantly inhibits cell proliferation, migration, and invasion through the blockade of the p38/ERK signaling pathway activation, as well as negatively binding to JAM-2, highlighting its potential as a therapeutic target for CC.

Keywords: apoptosis; cervical cancer; junctional adhesion molecule-2; miRNA-374b; migration; p38/ERK signaling pathway; siha cell proliferation.

MeSH terms

  • Adult
  • Apoptosis / genetics*
  • Base Sequence
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MAP Kinase Signaling System*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Up-Regulation / genetics
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology*
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Cell Adhesion Molecules
  • JAM2 protein, human
  • MIRN374 microRNA 374, human
  • MicroRNAs
  • p38 Mitogen-Activated Protein Kinases