Extracellular Vesicles-Mediated Transfer of miRNA Let-7b from PC3 Cells to Macrophages

Abstract

Prostate-derived extracellular vesicles (pEVs) may represent a way to selectively transport cargo molecules from the producing cells to the target cells to allow biological events, both in physiological and pathological circumstances. pEVs cargo participates in the modulation of the inflammatory responses in physiological conditions and during cancer progression. In the present study, we examined the expression levels of miRNA Let-7b, in both precursor and mature forms, in noncancerous and cancerous prostate cell lines, PNT2 and PC3 respectively, and in their extracellular vesicles (EVs) using reverse-transcription quantitative PCR strategies. We showed that miRNA Let-7b was highly expressed in noncancerous cells and strongly decreased in cancerous PC3 cells, while the opposite was observed in the respective EVs, thus supporting the tumor suppressor role of miRNA Let7-b. We also demonstrated that miRNA Let-7b can be transferred to THP-1 cells via EVs, which are known to induce TAM-like polarization. Our results support the view that miRNA Let-7 b, contained in PC3-derived EVs, is associated with the increase in the miRNA Let7-b observed in TAM-like macrophages. Overall, our results indicate that circulating EV-loaded miRNA might be useful biomarkers for prostate cancer progression and might also support a possible use of pEVs as targets for prostate cancer therapy.

Exosomes: Small vesicles with big roles in cancer, vaccine development, and therapeutics

“…Thus, packaging of tumor suppressor miRNAs in exosomes produced by cancer cells may be advantageous for their proliferation and guarantee the dissemination of pro-tumorigenic molecules into the microenvironment. Furthermore, the results confirmed that Let-7b was transferred to monocytic THP-1 cells through exosomes, influencing the polarization of tumor-associated macrophages (TAM) [ 88 ]. Other studies have revealed that tumor suppressor miR-26a can regulate the secretion of exosomes in prostate cancer cells by binding its target genes, SHC4 , PFDN4 , and CHORDC1 .…”

Natriuretic Peptides Regulate Prostate Cells Inflammatory Behavior: Potential Novel Anticancer Agents for Prostate Cancer

“…In particular, miRNA let-7b has been involved in the regulation of Toll-like receptor 4 (TLR4) expression, which, in turn, is responsible for NF-κB activation [42]. It has recently been shown that miRNA let-7b expression is reduced in prostate cancer PC3 cells [43], suggesting that the inhibitory mechanisms leading to the homeostatic control of NF-κB activation are dysregulated in advanced stage prostate cancer cells. Our results are in agreement with several studies demonstrating that NF-κB promotes cell survival, proliferation, and invasion in prostate cancer [5].…”

Regulation of Neuroendocrine-like Differentiation in Prostate Cancer by Non-Coding RNAs

“…  in PCa vs adjacent tissue [244,255]   migration, invasion, EMT [256]   proliferation, migration [255]  poor survival [244]  tissue:  predicts BCR [236]  regulated by lncRNA PAR [257] hsa-miR-363   in NEPC tissues [194 with an  in malignancy [233]   in PCa vs BPH [263]   in PCa [264] [265]   in PCa and metastases [266]   viability, migration, invasion [264]  overrides radiation-induced cell cycle arrest [267]  associated with disease recurrence [266] --  in PCa [199]   in patients with LN metastases [269]  promotes PCa progression [270,271]   expression predicts poor survival [272]  blood: BPH vs PCa   favors progression and self-renewal [129]   correlates with early clinical failure [286]  urine: cancer cellmacrophage signalling [287]  urine: PCa vs healthy [288]  negative regulation by lncRNA TTTY15 [289]  suppresses AR via Myc [290] in NED in vitro [228] --• PTEN [254] •…”

“…[249]  TP53 [250]   proliferation [245]  plasma: localized vs metastatic PCa [251]  urine: BCR [252]  urine, urine EVs, plasma: PCa vs BPH vs healthy [246]  biopsy: tumour vs adjacent tissue [253] -- PTEN [254]   in PCa vs adjacent tissue [244,255]   migration, invasion, EMT [256]   proliferation, migration [255]  poor survival [244]  tissue:  predicts BCR [236]  regulated by lncRNA PART1 [257] --  in recurrent PCa [258]   in young PCa patients [199]   in expression concomitantly   proliferation and EMT [259] -- miR-363 biogenesis regulated by IFIT5, downstream of IFNgammaantiviral response) [189] in NED from hypoxia [260] • 12 of 42 with an  in malignancy [233]   in PCa vs BPH [263]   in PCa [264] [265]   in PCa and metastases [266]   viability, migration, invasion [264]  overrides radiation-induced cell cycle arrest [267]  associated with disease recurrence [266] --  in PCa [199]   in patients with LN metastases [269]  promotes PCa progression [270,271]   expression predicts poor survival [272]  blood: BPH vs PCa   favors progression and self-renewal [129]   correlates with early clinical failure [286]  urine: cancer cellmacrophage signalling [287]  urine: PCa vs healthy [288]  negative regulation by lncRNA TTTY15 [289]  suppresses AR via Myc [290] in experimental NED…”

“…hsa-miR-93   in experimental NED [228] -- PTEN [268]   in PCa [199]   in patients with LN metastases [269]  promotes PCa progression [270,271]   expression predicts poor survival [272]  blood: BPH vs PCa [208]  seminal plasma: disease aggressiveness [ with an  in malignancy [233]   in PCa vs BPH [263]   in PCa [264] [265]   in PCa and metastases [266]   viability, migration, invasion [264]  overrides radiation-induced cell cycle arrest [267]  associated with disease recurrence [266] --  in PCa [199]   in patients with LN metastases [269]  promotes PCa progression [270,271]   expression predicts poor survival [272]  blood: BPH vs PCa [208]  seminal plasma: disease aggressiveness [273]  plasma: disease prediction [274]  serum: PCa diagnosis [275] -  in PCa [199]   in advanced PCa [260]   in patients with LN metastases [269]   invasiveness [279] - serum: disease stage and risk [233]  serum: decreased in cancer [280] -  in advanced PCa [285]   favors progression and self-renewal [129]   correlates with early clinical failure [286]  urine: cancer cellmacrophage signalling [287]  urine: PCa vs healthy [288]  negative regulation by lncRNA TTTY15 [289]  suppresses AR via Myc [290] in NEPC…”