MicroRNA-582-5p promotes triple-negative breast cancer invasion and metastasis by antagonizing CMTM8

Bioengineered. 2021 Dec;12(2):10126-10135. doi: 10.1080/21655979.2021.2000741.

Abstract

Triple-negative breast cancer (TNBC) commonly have aggressive properties. microRNA-582-5p (miR-582-5p) modulates the progression of several cancers. Yet, the role of miR-582-5p in TNBC progression is undetermined. In the current study, we investigated miR-582-5p expression levels and clinical significance in TNBC. The impact of miR-582-5p modulation on the biological behaviors of TNBC cells were measured. The downstream gene(s) regulated by miR-582-5p in TNBC was explored. We showed that compared to adjacent normal breast tissues, the miR-582-5p level was elevated in TNBC samples. The upregulation of miR-582-5p correlated with lymph node metastasis. Overexpression of miR-582-5p enhanced TNBC cell migration and invasion, whereas knockdown of miR-582-5p had an adverse impact on aggressive phenotype. In vivo xenograft mouse studies demonstrated that miR-582-5p overexpression accelerated TNBC growth and metastasis. Mechanistically, miR-582-5p selectively inhibited CMTM8, leading to a reduction of CMTM8 expression. CMTM8 showed suppressive effects on TNBC cell migration and invasion. Rescue experiments revealed that overexpression of CMTM8 impaired miR-582-5p-induced migration and invasion in TNBC cells. Overall, our data uncover an oncogenic role for miR-582-5p in TNBC metastasis through inhibition of CMTM8. We suggest miR-582-5p as a promising target for managing TNBC.

Keywords: Breast cancer; CMTM8; invasion; metastasis; miR-582-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MARVEL Domain-Containing Proteins / genetics
  • MARVEL Domain-Containing Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology*
  • Up-Regulation / genetics

Substances

  • CMTM8 protein, human
  • Chemokines
  • MARVEL Domain-Containing Proteins
  • MIRN582 microRNA, human
  • MicroRNAs
  • RNA, Messenger

Grants and funding

This work was supported by the Science and Technology Plan Project of Liaoning Province (20180540129 and 20180530095), Science and Technology Plan Project of Shenyang (19-104-4-035), the Personnel Training Project of Liaoning Cancer Hospital & Institute of China (201703). The Medical-Industry Interdisciplinary Research Fund Project of Liaoning Cancer Hospital and Dalian University of Technology (LD202005 and LD202025) and the Key Laboratory of Tumor Radiosensitization and Normal Tissue Radioprotection Project of Liaoning Province (No. 2018225102). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.