Prostate cancer is the second most common cancer and the second leading cause of cancer-related death in men in the United States. Based on recent data, it is estimated that, in 2013, nearly 239,000 men will be diagnosed with prostate cancer, and nearly 30,000 men will die of the disease. Furthermore, it is estimated that approximately $11.9 billion is spent each year in the United States on prostate cancer treatment.

This is why findings by Cincinnati Cancer Center researchers, showing that a tumor suppressive microRNA, when activated by an anti-estrogen drug, could contribute to development of future targeted therapies, are creating lots of interest and excitement. These findings are published in the May 16, 2014 edition of the journal PLOS ONE.

Regulating gene expression
“MicroRNAs, or miRNAs, are short RNA molecules that play a prominent role in regulating gene expression. One miRNA can target multiple genes, but their expression is often hijacked by cancer cells and disrupts multiple cancer-causing or tumor-suppressing pathways,” noted Shuk-Mei Ho, PhD, director of the CCC and Jacob G. Schmidlapp Chair of Environmental Health and professor at the University of Cincinnati (UC) College of Medicine.


…. this highlights the potential use of this anti-estrogen or miRNA in patients with recurrent prostate cancer for whom there is no treatment…


New miRNA
Ho, along with Ricky Y.K. Leung, PhD, member of the CCC, assistant research professor in the department of environmental health and member of the UC Cancer Institute, and their team identified a new miRNA, known as hsa-miR-765, which is specifically activated by the anti-estrogen drug fulvestrant (ICI-182,780; Faslodex?; AstraZeneca)

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“This miRNA suppresses expression of HMGA1, a gene that was shown in previous studies to be associated with prostate cancer progression and recurrence,” Leung explained. “These findings do not only contribute to new insights on the effects of anti-estrogen but also the potential of using miRNA for monitoring drug efficacy and for future RNA-based therapy developments.

Preventing or Slowing progression
“This study also highlights the potential use of this anti-estrogen or miRNA in patients with recurrent prostate cancer, for whom there is no treatment, and raises the possibility of using anti-estrogen or miRNA treatments in preventing or slowing progression for primary prostate cancer.”

Using cultured prostate cancer specimens from patients who were given a single 250 mg dose of fulvestrant, researchers found that hsa-miR-765 acted as a tumor suppressor when its expression was increased by the use of the drug. “Both the anti-estrogen and the hsa-miR-765 mimic suppressed HMGA1 protein expression,” Ho noted. “Levels of hsa-miR-765 were increased, and HMGA1 expression was almost completely lost in prostate cancer specimens from patients treated with a single dose of fulvestrant 28 days before removal of their prostate glands.”These findings reveal a unique fulvestrant signaling process involving the increased regulation of hsa-miR-765 that suppresses the HMGA1 protein as part of the mechanism underlying the tumor suppressor action in prostate cancer. This could lead to newer treatment options with less toxicity for these patients.”

For more information:
Leung YK, Chan QKY, Ng CF, Ma FMT, Tse HM, To KF, Maranchie J, Ho SM, Lau KM. Hsa-miRNA-765 as a Key Mediator for Inhibiting Growth, Migration and Invasion in Fulvestrant-Treated Prostate Cancer, PLOS ONE, 16 May 2014, 10.1371/journal.pone.0098037. [Article] .

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