miR-4732-5p promotes breast cancer progression by targeting TSPAN13

J Cell Mol Med. 2019 Apr;23(4):2549-2557. doi: 10.1111/jcmm.14145. Epub 2019 Jan 31.

Abstract

MiR-4732-5p was previously found to be dysregulated in nipple discharge of breast cancer. However, the expression and function of miR-4732-5p in breast cancer remain largely unknown. Here, the expression of miR-4732-5p was detected using quantitative real-time PCR in breast cancer tissues and cell lines. Cell proliferation, apoptosis, migration and invasion assays were performed to examine the effects of miR-4732-5p in breast cancer. In addition, mRNA sequencing, bioinformatics analysis, Western blot and luciferase assays were performed to identify the target of miR-4732-5p. Overall, miR-4732-5p was significantly down-regulated in breast cancer tissues, especially in lymph node metastasis (LNM)-negative tissues, compared with adjacent normal tissues. However, it was more highly expressed in LNM-positive breast cancer tissues, compared with LNM-negative ones. Expression of miR-4732-5p was positively correlated with lymph node metastasis, larger tumour size, advanced clinical stage, high Ki-67 levels and poor prognosis. MiR-4732-5p promoted cell proliferation, migration and invasion in breast cancer. MiR-4732-5p directly targeted the 3'-UTR of tetraspanin 13 (TSPAN13) and suppressed TSPAN13 expression at the mRNA and protein levels. These results suggested that miR-4732-5p may serve as a tumour suppressor in the initiation of breast cancer, but as a tumour promoter in breast cancer progression by targeting TSPAN13.

Keywords: TSPAN13; breast cancer; metastasis; miR-4732-5p; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Aged, 80 and over
  • Antagomirs / genetics
  • Antagomirs / metabolism
  • Apoptosis / genetics
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphatic Metastasis
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • Signal Transduction
  • Survival Analysis
  • Tetraspanins / genetics*
  • Tetraspanins / metabolism

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • MicroRNAs
  • Oligoribonucleotides
  • TSPAN13 protein, human
  • Tetraspanins