miR-100-5p inhibition induces apoptosis in dormant prostate cancer cells and prevents the emergence of castration-resistant prostate cancer.

Abstract

Carcinoma of the prostate is the most common cancer in men. Treatment of aggressive prostate cancer involves a regiment of radical prostectomy, radiation therapy, chemotherapy and hormonal therapy. Despite significant improvements in the last decade, the treatment of prostate cancer remains unsatisfactory, because a significant fraction of prostate cancers develop resistance to multiple treatments and become incurable. This prompts an urgent need to investigate the molecular mechanisms underlying the evolution of therapy-induced resistance of prostate cancer either in the form of castration-resistant prostate cancer (CRPC) or transdifferentiated neuroendocrine prostate cancer (NEPC). By analyzing micro-RNA expression profiles in a set of patient-derived prostate cancer xenograft tumor lines, we identified miR-100-5p as one of the key molecular components in the initiation and evolution of androgen ablation therapy resistance in prostate cancer. In vitro results showed that miR-100-5p is required for hormone-independent survival and proliferation of prostate cancer cells post androgen ablation. In Silico target predictions revealed that miR-100-5p target genes are involved in key aspects of cancer progression, and are associated with clinical outcome. Our results suggest that mir-100-5p is a possible therapeutic target involved in prostate cancer progression and relapse post androgen ablation therapy.

• Authors: Noushin Nabavi, Nur Ridzwan Nur Saidy, Erik Venalainen, Anne Haegert, Abhijit Parolia, Hui Xue, Yuwei Wang, Rebecca Wu, Xin Dong, Colin Collins, Francesco Crea, Yuzhuo Wang
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 4079 (06 22 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28642484 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androgens
• MIRN100 microRNA, human
• MicroRNAs

Topics

• Androgens (metabolism)
• Animals
• Apoptosis (genetics)
• Cell Cycle (genetics)
• Cell Line, Tumor
• Cell Proliferation
• Disease Models, Animal
• Disease Progression
• Gene Expression Profiling
• Humans
• Male
• Mice
• MicroRNAs (genetics)
• Prostatic Neoplasms, Castration-Resistant (genetics, metabolism, pathology)
• RNA Interference
• Signal Transduction