Urinary-exosomal miR-2909: A novel pathognomonic trait of prostate cancer severity

Cancer cells govern miR‐2909 exosomal recruitment through its 3′‐end post‐transcriptional modification

“…The 3′‐end adenylated miRNAs were found to be relatively enriched in cells, whereas 3′‐end uridylated isoforms were overrepresented in the exosomes . The recruitment of miR‐2909 into urinary exosomes assumed great importance by our recent findings that unambiguously demonstrated that urinary‐exosomal miR‐2909 not only has the ability to differentiate between bladder and prostate cancer but may also even be more useful as a pathognomonic factor reflecting the aggressiveness of prostate cancer . By employing archetype cancer‐cellular models, we report that most of the cancer cells (from different tissue origin) have the ability to recruit miR‐2909 into their secreted exosomes, and the underlying mechanism of this miRNA recruitment is the increased ratio of 3′‐end uridylation to adenylation of miR‐2909 in these cancer cells.…”

“…15 The recruitment of miR-2909 into urinary exosomes assumed great importance by our recent findings that unambiguously demonstrated that urinary-exosomal miR-2909 not only has the ability to differentiate between bladder and prostate cancer but may also even be more useful as a pathognomonic factor reflecting the aggressiveness of prostate cancer. 16 By employing archetype cancer-cellular models, we report that most of the cancer cells (from different tissue origin) have the ability to recruit miR-2909 into their secreted exosomes, and the underlying mechanism of this miRNA recruitment is the increased ratio of 3′-end uridylation to adenylation of miR-2909 in these cancer cells. Further, proteomic analysis of the secreted exosomes (by the cells employed in the present study) revealed that distribution of adenosine kinase between the cells and exosomes may be crucial for the type of post-transcriptional modification of miR-2909 and subsequent recruitment to either cellular cytoplasm or released exosomes.…”

Role of miR-2909 in Prostate Carcinogenesis

“…In contrast, miR-615-3p was significantly recruited to urinary exosomes in subjects suffering from both bladder and PCa compared to those found in either healthy-control subjects or disease-control subjects suffering from BPH. Elucidating the correlation of urinary exosomal miRNAs with PCa severity, the extent of miR-2909 recruitment to the urinary exosomes showed significant correlation with the severity of PCa based on Gleason Score within different subgroups grouped into Hormone-sensitive or Hormoneinsensitive or Hormone-naive groups [39]. Further, in this study, it was reported that the serum PSA levels did not correlate with the severity of PCa either in Hormone-sensitive or Hormoneinsensitive subjects.…”

“…Various studies have reported a change in the content of freely circulating exosomal miRNAs during tumorigenesis reflecting the situation in the tumor [38]. Samina et al [39] studied the relative urinary exosomal recruitment levels of two miRNAs, that is, mir-2909 & miR-615-3p in human subjects suffering from either bladder cancer or PCa. Urinary exosomes, derived from human subjects suffering from PCa, were found to be enriched with miR-2909 compared to those derived from either healthy control subjects or benign prostatic hyperplasia (BPH) subjects or patients with urinary bladder cancer.…”

Extracellular vesicles in urologic malignancies—Implementations for future cancer care

“…[136][137][138][139] Moreover, on the basis of the mass spectrometry proteome analysis, thousands of proteins encapsulated on and within vesicles are identified as biomarker candidates from urinary EVs or cell lines of PCa, [139][140][141][142][143][144][145][146] whereas the value as biomarkers is still controversial, and several types of research regenerate the previous biomarkers by the using targeted proteomics and immuno-assays. 134 Based on a proximity ligation assay, PC-derived EVs in blood has also shown to contain proteins specific to PCa, such as phosphatase 151 Donovan et al 152 Hendriks et al 153 Motamedinia et al 154 Royo et al 155 (Continues) sequencing reveals the potential values for miRNA served as diagnostic and prognostic biomarkers for PCa within serum or plasma EVs, 41,131,132,[158][159][160][161][162] such as miR-141 and miR-375 in serum, have been correlated with metastatic PCa. 159,163 Another study indicates that exosomal miR-1290 and miR-375 could be as prognostic markers in castration-resistant prostate cancer (CRPC).…”