Identification of androgen-responsive microRNAs and androgen-related genes in breast cancer

Anticancer Res. 2013 Nov;33(11):4811-9.

Abstract

Background: Androgen receptors (ARs) are expressed in many breast cancer cells, but the mechanism of action of androgens is not as well-characterized as in other cell types. The study of microRNAs has recently provided with important insights into the biology of hormone-dependent cancer.

Materials and methods: We attempted to identify microRNAs induced by dihydrotestosterone in an AR-positive cell line. We examined a possible correlation among microRNAs, target genes, and ARs in breast cancer tissues using immunohistochemistry and laser capture microscopy.

Results: Our analysis demonstrated that miR-363 and its possible target IQ motif and WD repeats-1 (IQWD1) are involved in a microRNA-mRNA pathway related to the mechanism of action of androgens. Our analyses showed that a high tumor level of IQWD1 in patients with breast cancer was significantly associated with adverse clinical outcomes.

Conclusion: Our findings indicated that the recruitment of IQWD1 to ARs may be a prerequisite for the growth stimulation by androgens through ARs in breast cancer cells.

Keywords: Breast cancer; IQWD1; androgen; microRNA.

Publication types

  • Comparative Study

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Androgens / pharmacology
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / drug therapy
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology
  • Case-Control Studies
  • Cell Proliferation
  • Dihydrotestosterone / pharmacology*
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Humans
  • Immunoenzyme Techniques
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Staging
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Tumor Cells, Cultured
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Androgens
  • Biomarkers, Tumor
  • DCAF6 protein, human
  • MIRN363 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Messenger
  • Receptors, Androgen
  • Dihydrotestosterone