MicroRNA-132-3p inhibits tumor malignant progression by regulating lysosomal-associated protein transmembrane 4 beta in breast cancer

Cancer Sci. 2019 Oct;110(10):3098-3109. doi: 10.1111/cas.14164. Epub 2019 Aug 19.

Abstract

Lysosomal-associated protein transmembrane 4 beta (LAPTM4B), a proto-oncogene, has been shown to be a positive modulator in cancer progression. However, the mechanism of LAPTM4B regulation is not fully elucidated. Aberrant microRNAs (miRNAs) can regulate gene expression by interfering with target transcripts and/or translation to exert tumor-suppressive or oncogenic effects in breast cancer. In the present study, miR-132-3p, which was predicted by relevant software, was confirmed to directly bind to the 3' untranslated region (3'UTR) of LAPTM4B and negatively regulate its expression in luciferase reporter and western blot assays. Subsequently, we validated that miR-132-3p was downregulated in breast cancer tissues. Receiver-operating characteristic curve analysis indicated that miR-132-3p had accurate diagnostic value, and a Kaplan-Meier and Cox regression model showed that miR-132-3p was a potential prognostic marker for recurrence, showing low levels in breast cancer patients. In addition, we showed that miR-132-3p was inversely correlated with LAPTM4B expression in the above samples. Functionally, miR-132-3p suppressed the migration and invasion of breast carcinoma cells through LAPTM4B by mediating epithelial-mesenchymal transition signals, and partially reversed the carcinogenic effects of LAPTM4B by inhibiting the PI3K-AKT-mTOR signaling pathway. Taken together, these findings provide the first comprehensive analysis of miR-132-3p as a direct LAPTM4B-targeted miRNA, and shed light on miR-132-3p/LAPTM4B as a significant functional axis involved in the oncogenesis and metastasis of breast cancer.

Keywords: LAPTM4B; breast cancer; metastasis; miR-132-3p; regulation.

MeSH terms

  • 3' Untranslated Regions
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism*
  • Proto-Oncogene Mas
  • ROC Curve
  • Signal Transduction
  • Survival Analysis

Substances

  • 3' Untranslated Regions
  • LAPTM4B protein, human
  • MAS1 protein, human
  • MIRN132 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Oncogene Proteins
  • Proto-Oncogene Mas