miRNA as Regulators of Prostate Carcinogenesis and Endocrine and Chemoresistance

Abstract

More therapy options are available for advanced prostate cancer, including novel inhibitors of androgen synthesis, anti-androgens, chemotherapeutics and targeted therapies. Although patients ´ survival has been improved, management of castration therapy-resistant prostate cancer remains a challenge. Regulation of cellular events in cancer by small non-coding miRNAs is, therefore, an area of special interest. Overexpression of selected miRNA may lead to androgen independence and prostate cancer progression. miRNA may be considered also a biomarker in patients with prostate cancer. In contrast, diminished expression of tumor-suppressive miRNA in prostate cancer leads to enhanced proliferation, reduced apoptosis, increased migration, invasion and epithelial- to-mesenchymal transition. miRNA may be directly involved in the regulation of chemosensitivity in prostate cancer. Experimental overexpression of selected miRNA in chemoresistant prostate cancer leads to the inhibition of cellular stemness and epithelial-to-mesenchymal transition. Reduction of tumor-suppressive miRNA may also lead to hyperactivity of signaling pathways such as that of the epidermal growth factor receptor and mitogen-activated protein kinase. Although considerable progress on miRNA research in prostate cancer has been achieved, therapeutic effects could be improved on the basis of the development of novel delivery methods.