MiR-4524b-5p/WTX/β-catenin axis functions as a regulator of metastasis in cervical cancer

PLoS One. 2019 Apr 2;14(4):e0214822. doi: 10.1371/journal.pone.0214822. eCollection 2019.

Abstract

Cervical cancer is the second most deadly gynecological tumor worldwide. MicroRNAs (miRNAs) play very important roles in tumor oncogenesis and progression. The mechanism of post-transcription regulation of WTX gene is still unknown. A series of differential miRNAs were discovered by microarray analysis comparing three pairs of primary cervical cancer specimens and their relapsed tumors from three patients. Quantitative reverse transcriptase PCR (qRT-PCR), Western Blot (WB) and Immunohistochemistry (IHC) was used to detect the expression of miR-4524b-5p and WTX in cervical cell lines and tissues. The biological function of miR-4524b-5p and WTX was investigated through knockdown and overexpression with inhibitor/siRNA and mimic/plasmid in vitro and in vivo. In this study, we found that miR-4524b-5p is highly expressed in relapsed cervical cancer specimens. Combined in vitro and in vivo experiments, showed that miR-4524b-5p could regulate the migration and invasion ability of cervical cancer. Furthermore, we also found that miR-4524b-5p could regulate the migration and invasion of cervical cancer by targeting WTX and that WTX could regulate the expression of β-catenin. Taken together, our data identified a miR-4524b-5p/WTX/β-catenin regulatory axis for cervical cancer, and miR-4524b-5p may be a potential target for cervical cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Female
  • Gene Knockdown Techniques
  • Heterografts
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Transplantation
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*
  • beta Catenin / metabolism*

Substances

  • AMER1 protein, human
  • Adaptor Proteins, Signal Transducing
  • CTNNB1 protein, human
  • MicroRNAs
  • Tumor Suppressor Proteins
  • beta Catenin

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (no. 81572900), the National Key R&D Program of China, Stem Cell and Translation Research (no. 2016YFA0102000), the Key Project of Hunan Province 2016 (no. 2016JC2036), the Fundamental Research Funds for the Central Universities of Central South University (no. 1053320171187), and the Hunan Provincial Natural Science Foundation of China (no. 2017JJ3513).