The MicroRNA-382-5p/MXD1 Axis Relates to Breast Cancer Progression and Promotes Cell Malignant Phenotypes

J Surg Res. 2020 Feb:246:442-449. doi: 10.1016/j.jss.2019.09.018. Epub 2019 Oct 18.

Abstract

Background: MicroRNA (miRNA)-382-5p functions as an oncogenic miRNA in breast cancer. MXD1 was demonstrated to be one of its direct targets. However, the involvement of miRNA-382-5p/MXD1 axis in breast cancer remains unknown. The aim of this study was to investigate the expression pattern, clinical significance, and potential functions of miRNA-382-5p/MXD1 axis in breast cancer.

Materials and methods: Quantitative polymerase chain reaction was performed to detect the expression levels of miRNA-382-5p and MXD1 messenger RNA (mRNA) in 96 pairs of breast cancer and matched noncancerous breast tissue samples from the same patients. Relationships between miRNA-382 expression, MXD1 expression, and combined miRNA-382-5p and MXD1 expression, and various clinicopathological characteristics of breast cancer were statistically evaluated, and their roles in breast cancer cell proliferation and invasion were also examined.

Results: Compared with noncancerous breast tissues, miRNA-382-5p expression was upregulated but MXD1 mRNA expression was downregulated in breast cancer tissues (both P < 0.01). High miRNA-382 expression, MXD1 expression, and combined miRNA-382-5p and low MXD1 expression were significantly associated with advanced tumor stage and the presence of lymph node metastasis (all P < 0.05). Overexpression of miRNA-382-5p dramatically reduced MXD1 mRNA and protein expression levels in breast cancer cells. miRNA-382-5p upregulation markedly enhanced breast cancer cell proliferation and invasion, while its downregulation inhibited these malignant phenotypes of breast cancer cells in vitro. Notably, overexpressed MXD1 reversed the effects of upregulated miRNA-382-5p on cell proliferation and invasion in vitro.

Conclusions: The dysregulation of miRNA-382-5p-MXD1 axis may be involved in the development and aggressive progression of breast cancer. miRNA-382-5p may target MXD1, leading to cell invasion and proliferation in breast cancer cells in vitro, implying its potentials as a therapeutic target for this type of cancer.

Keywords: Breast cancer; Clinicopathologic characteristics; Invasion; MXD1; Proliferation; microRNA-382-5p.

MeSH terms

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Breast / pathology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MCF-7 Cells
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • MIRN382 microRNA, human
  • MXD1 protein, human
  • MicroRNAs
  • RNA, Messenger
  • Repressor Proteins