High miR-205 expression in normal epithelium is associated with biochemical failure - an argument for epithelial crosstalk in prostate cancer?

Abstract

Due to insufficient prognostic tools, failure to predict aggressive prostate cancer (PC) has left patient selection for radical treatment an unsolved challenge. This has resulted in overtreatment with radical therapy. Better prognostic tools are urgently warranted. MicroRNAs (miRs) have emerged as important regulators of cellular pathways, resulting in altered gene expressions. miR-205 has previously been observed downregulated in PC, acting as tumor suppressor. Herein, the expression of miR-205 in prostate tissue was examined in a large, well-described cohort of 535 Norwegian prostatectomy patients. Using in situ hybridization, miR-205 expression was semiquantatively measured in normal and tumor tissues from radical prostatectomy specimens. Associations with clinicopathological data and PC relapse were calculated. Expression of miR-205 was lower in tumor epithelium compared to normal epithelium. No association was observed between miR-205 expression in primary tumor epithelium and cancer relapse. In contrast, high expression of miR-205 in normal epithelium was independently associated with biochemical relapse (HR = 1.64, p = 0.003). A prognostic importance of miR-205 expression was only found in the normal epithelium, raising the hypothesis of epithelial crosstalk between normal and tumor epithelium in PC. This finding supports the proposed novel hypothesis of an anti-cancerogenous function of normal epithelium in tumor tissue.

miRNA-205 Nanoformulation Sensitizes Prostate Cancer Cells to Chemotherapy

“…Many studies demonstrate that prostate cancer cell lines and tumor cells exhibit suppressed miR-205 levels [ 24 ]. miR-205 loss is highly associated with tumor growth, invasion, and migration of cancer cells [ 25 ].…”

Five microRNAs in serum as potential biomarkers for prostate cancer risk assessment and therapeutic intervention

“…Whole genome expression profiling was previously used to identify possible roles for miRNAs 1234, 1238, 1913, 489-5p, 1825, 484, and 483-5p in the development, progression, or suppression of PCa [ 5 ]. Additionally, miR-205 is mainly expressed on the basal cells of prostate tissue, and inhibits the targets of zinc finger E-box-binding proteins, PKCε and HMGB3 to inhibit tumor proliferation and apoptosis and cancer cell aggressiveness [ 6 , 7 ]. The let-7 family may also play an important role in the recurrence and metastasis of PCa by regulating tumor stem cells [ 8 ].…”

A basal‐enriched microRNA is required for prostate tumorigenesis in a Pten knockout mouse model

“…pAkt and Pten levels are linked to prostate tumorigenesis in a dosage dependent manner . Furthermore, a recent survey of miR‐205 expression in prostate cancer patients indicates an association between high miR‐205 expression in normal epithelium and relapse . Thus, maintaining miR‐205 expression may be important to the initiation and progression of prostate cancer.…”

“…25 Furthermore, a recent survey of miR-205 expression in prostate cancer patients indicates an association between high miR-205 expression in normal epithelium and relapse. 28 Thus, maintaining miR-205 expression may be important to the initiation and progression of prostate cancer. Indeed, loss of miR-205 in the Pten null background reduces global pAkt levels by~50% ( Figure 5B).…”