MicroRNA-384 inhibits the progression of breast cancer by targeting ACVR1

Oncol Rep. 2018 Jun;39(6):2563-2574. doi: 10.3892/or.2018.6385. Epub 2018 Apr 20.

Abstract

Breast cancer is the leading cause of cancer-related deaths in females worldwide. Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancer cases and has a poorer prognosis than other subtypes. Moreover, the treatment for breast cancer, especially for TNBC, remains unsatisfactory. Therefore, novel therapies are urgently needed. Microribonucleic acids (miRNAs) are a class of biomarkers and therapeutic targets in many types of cancers. In the present study, the expression of miR-384 was explored in GSE58606 and in fresh breast cancer tissues by qPCR. The results showed that miR-384 was decreased in breast cancer, especially in TNBC. The results of MTT, colony formation, soft agar, Transwell migration, wound healing and the tumorigenesis assay demonstranted that overexpression of miR-384 inhibited the proliferation and migration of breast cancer in vitro and in vivo; knockdown of miR-384 enhanced the proliferation and migration of breast cancer. In addition, luciferase assay showed that Activin A receptor type 1 (ACVR1) was a direct target of miR-384 and is involved in the inhibitory effects of miR-384 on breast cancer progression. Furthermore, this study indicated that ACVR1 activated the Wnt/β-catenin signaling pathway in breast cancer. In conclusion, our findings revealed functional and mechanistic links between miR-384 and ACVR1 in the progression of breast cancer. miR-384 not only plays an important role in the progression of breast cancer, but has promise as a potential therapeutic target for breast cancer especially for TNBC.

MeSH terms

  • 3' Untranslated Regions
  • Activin Receptors, Type I / genetics*
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Down-Regulation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Transplantation
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology*
  • Wnt Signaling Pathway

Substances

  • 3' Untranslated Regions
  • MIRN384 microRNA, human
  • MicroRNAs
  • ACVR1 protein, human
  • Activin Receptors, Type I