BRD7-Mediated miR-3148 Inhibits Progression of Cervical Cancer by Targeting Wnt3a/β-Catenin Pathway

Reprod Sci. 2020 Mar;27(3):877-887. doi: 10.1007/s43032-019-00091-8. Epub 2020 Jan 6.

Abstract

Abnormal expression of miRNAs is closely related to the occurrence and development of tumors, and thus has become the most concerned biomolecule in the field of tumors. But so far, miRNAs that are truly recognized and studied for their function are only a small part, and their mechanism in tumors needs to be further studied. In this study, we identify that miR-3148 is downregulated in the development of cervical cancer. In cervical cancer cells, upregulated miR-3148 inhibits cell proliferation and promotes apoptosis, suggesting that miR-3148 acts as a tumor suppressor gene. Furthermore, we explored the mechanism of miR-3148 in cervical cancer cells from both transcriptional and post-transcriptional levels. Our research reveals that on the one hand, bromodomain containing 7 (BRD7) acts as a transcription factor to up-regulate the expression of miR-3148 at the transcriptional level; on the other hand, miR-3148 targets the 3'UTR of Wnt3a mRNA to inhibit Wnt3a expression at the post-transcriptional level, thereby suppressing Wnt3a/β-catenin signaling pathway and exerting its tumor suppressor role in cervical cancer. In conclusion, our study elucidates the mechanism of BRD7/miR-3148/Wnt3a/β-catenin pathway in cervical cancer and provides a new research direction for targeted therapy of cervical cancer.

Keywords: BRD7; Cervical cancer; Wnt3a/β-catenin pathway; miR-3148.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Chromosomal Proteins, Non-Histone / metabolism
  • Disease Progression
  • Female
  • Gene Expression Regulation*
  • Humans
  • MicroRNAs / metabolism*
  • Uterine Cervical Neoplasms / metabolism*
  • Wnt Signaling Pathway*

Substances

  • BRD7 protein, human
  • Chromosomal Proteins, Non-Histone
  • MIRN3148 microRNA, human
  • MicroRNAs