MicroRNA-99a inhibits tumor aggressive phenotypes through regulating HOXA1 in breast cancer cells

Oncotarget. 2015 Oct 20;6(32):32737-47. doi: 10.18632/oncotarget.5355.

Abstract

MicroRNAs (miRNAs) are key regulators of tumor progression. Based on microarray data, we identified miR-99a as a potential tumor suppressor in breast cancer. Expression of miR-99a is frequently down-regulated in breast cancer tissues relative to normal breast tissues. Reduced miR-99a expression was highly associated with lymph node metastasis and shorter overall survival of patients with breast cancer. Gain- and loss-of-function studies revealed that, miR-99a significantly inhibits breast cancer cell proliferation, migration, and invasion. An integrated bioinformatics analysis identified HOXA1 mRNA as the direct functional target of miR-99a, and this regulation was confirmed by luciferase reporter assay. Furthermore, we showed for the first time that HOXA1 expression is elevated in breast cancer tissues. Knockdown of HOXA1 significantly inhibited breast cancer cell proliferation, migration and invasion, and restoration of HOXA1 partially rescued the inhibitory effect of miR-99a in breast cancer cells. Collectively, our data indicate that miR-99a plays a tumor-suppressor role in the development of breast cancer, and could serve as a potential therapeutic target for breast cancer treatment.

Keywords: HOXA1; breast cancer; invasion; miR-99a; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Base Sequence
  • Binding Sites
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Movement*
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Lymphatic Metastasis
  • MCF-7 Cells
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Molecular Sequence Data
  • Neoplasm Invasiveness
  • Phenotype
  • RNA Interference
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Survival Analysis
  • Time Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection

Substances

  • 3' Untranslated Regions
  • Homeodomain Proteins
  • MIRN99 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Transcription Factors
  • homeobox A1 protein