MicroRNA-148a promotes apoptosis and suppresses growth of breast cancer cells by targeting B-cell lymphoma 2

Anticancer Drugs. 2017 Jul;28(6):588-595. doi: 10.1097/CAD.0000000000000498.

Abstract

MicroRNAs (miRNAs) contribute toward tumorigenesis through the modulation of tumor-related genes. MiR-148a has been characterized as a tumor-suppressing miRNA and its downregulation has been reported in tumors of a variety of cancers. However, the functional role of miR-148a in breast cancer is not yet fully understood. Using both in-vitro and in-vivo models, we confirmed that miR-148a acts to inhibit the proliferation of breast cancer cells. Through the use of bioinformatic approaches in miRNA target prediction, we determined that B-cell lymphoma 2 (BCL-2) is a likely target of miR-148a. The overexpression and tumorigenic effects of BCL-2 have already been confirmed in cancerous tumors of the breast. A dual-luciferase assay was performed to confirm that miR-148a targets the 3'-untranslated region of BCL-2. In this study, we first characterized the downregulation of miR-148a in breast cancer tissues. We then found that restoring expression of miR-148a suppressed the expression of BCL-2 at the level of both mRNA and protein. Upregulation of miR-148a caused a subsequent reduction of proliferation and an increase in apoptosis. In conclusion, we have confirmed the role of miR-148a as a pivotal regulator in breast cancer through its targeting of BCL-2. This evidence strongly suggests that miR-148a could prove to be a novel therapeutic target in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • Down-Regulation
  • Female
  • Heterografts
  • Humans
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / therapy
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / administration & dosage
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Transfection

Substances

  • BCL2 protein, human
  • MIRN148 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2