MicroRNA-133a acts as a tumour suppressor in breast cancer through targeting LASP1

Oncol Rep. 2018 Feb;39(2):473-482. doi: 10.3892/or.2017.6114. Epub 2017 Nov 27.

Abstract

Many microRNAs (miRs) have been demonstrated to play promoting or tumor suppressive roles in human cancers including breast cancer. However, the molecular mechanism of miR-133a underlying the malignant progression of breast cancer still remains obscure. In the present study we observed that the expression of miR-133a was significantly downregulated in breast cancer tissues and cell lines, when compared with adjacent non-tumor tissues and normal breast cell line, respectively. Reduced miR-133a levels were significantly associated with advanced clinical stage, lymph node metastasis, as well as shorter survival time of patients with breast cancer. Restoration of miR-133a expression led to significant decrease in the proliferation, migration, and invasion of SK-BR-3 and MDA-MB-231 cells in vitro, as well as in tumor xenograft growth in nude mice. Luciferase reporter gene assay data identified LASP1 as a target gene of miR-133a, and the expression of LASP1 was negatively regulated by miR-133a in breast cancer cells. LASP1 was significantly upregulated in breast cancer tissues and cell lines, and its upregulation was significantly associated with disease progression. siRNA-induced LASP1 downregulation caused a significant reduction in breast cancer cell proliferation, migration and invasion. Furthermore, overexpression of LASP1 impaired the suppressive effects of miR-133a upregulation on the proliferation, migration and invasion of SK-BR-3 and MDA-MB-231 cells. In summary, the present study demonstrates that miR-133a acts as a tumor suppressor in breast cancer partly at least via targeting LASP1, and thus suggests that the miR-133a/LASP1 axis may become a potential therapeutic target for breast cancer.

Publication types

  • Retracted Publication

MeSH terms

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cytoskeletal Proteins / genetics*
  • Disease Progression
  • Down-Regulation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • LIM Domain Proteins / genetics*
  • MCF-7 Cells
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Survival Analysis

Substances

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • LASP1 protein, human
  • LIM Domain Proteins
  • MIRN133 microRNA, human
  • MicroRNAs