microRNA and non-canonical TGF-β signalling: implications for prostate cancer therapy

Crit Rev Oncol Hematol. 2014 Oct;92(1):49-60. doi: 10.1016/j.critrevonc.2014.05.011. Epub 2014 Jun 9.

Abstract

The incidence of prostate cancer is increasing worldwide and marks a significant health issue. Paired with this, current therapeutic options for advanced prostate cancer, notably androgen deprivation therapy (ADT), fail to provide a consistent level of efficacy throughout the treatment period, highlighting the need for new robust therapies. Growth factors, such as Transforming Growth Factor-beta (TGF-β), possess the ability to impede cancer development in the early stages, via alterations in either apoptosis, cell proliferation, or the promotion of cellular senescence. However, later in the pathogenesis, advanced prostate cancer cells become insensitive to the previously beneficial effects of TGF-β. The molecular mechanisms behind this acquired insensitivity are not well understood. Thus, the aim of this review is to examine the effects of a class of small non-coding RNA, microRNA (miRNA), on TGF-β signalling. The impact of miRNA on the canonical TGF-β Smad signalling pathway has been well investigated, hence, in this review, we will examine whether miRNA targeting members of non-canonical TGF-β signalling members, such as, Erk, RhoA, PI3K/Akt and JNK/p38 could provide alternate therapeutic options for advanced prostate cancer.

Keywords: Prostate cancer; Smad signalling; TGF-β superfamily; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Progression
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Staging
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / therapy
  • Signal Transduction*
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta / metabolism*

Substances

  • Intercellular Signaling Peptides and Proteins
  • MicroRNAs
  • Smad Proteins
  • Transforming Growth Factor beta