A microRNA code for prostate cancer metastasis

Bonci, Desirée; Coppola, Valeria; Patrizii, Michele; Addario, Antonio; Cannistraci, Alessio; Francescangeli, Federica; Pecci, Raffaella; Muto, Giovanni; Collura, Devis; Bedini, Rossella; Zeuner, Ann; Valtieri, Mauro; Sentinelli, Steno; Benassi, Maria Serena; Gallucci, Michele; Carlini, Paolo; Piccolo, Stefano; Maria, Ruggero De

doi:10.1038/onc.2015.176

Cited by 117 publications

(79 citation statements)

References 66 publications

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“…No other studies to our knowledge have investigated the effects of miR-15a/16 on TGF-beta3 in pathological mechanisms of diabetic retinopathy. Previous studies, instead, have shown roles of miR-15 and -16 on TGF-beta signaling in other types of disorders, as miR-15/16 upregulated TGF-beta signaling, leading to progression of prostate cancer (Bonci et al, 2016). miR-16 overexpression suppressed TGF-beta release in human alveolar epithelial cells (Tamarapu Parthasarathy et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

miR-15a/16 inhibits TGF-beta3/VEGF signaling and increases retinal endothelial cell barrier proteins

Liu

Steinle

2017

Vision Research

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Hyperglycemia is a significant risk factor for diabetic retinopathy and induces multiple biochemical changes, including inflammation and endothelial dysfunction in the retina. Alterations in microRNA expression have been implicated in the pathological responses of diabetic retinopathy and the manipulation of microRNA may provide powerful strategy for therapeutics. Among the predicted targets of miR-15a and -16 are TGF-beta3, SMAD2/3, and VEGF, all of which are known to play a role in vascular endothelial functions. The purpose of this study was to investigate the hypothesis that miR-15a/16 inhibits TGF-beta3/VEGF signaling to maintain retinal endothelial cell barrier protein levels. Human primary retinal endothelial cells (REC) were maintained in normal (5 mM) glucose or transferred to high glucose medium (25 mM) for 3 days. REC were transfected with miRNA mimics (hsa-miR-15a-5p and -16-5p). Retinal lysates from miR-15a-transgenic mice were also analyzed. We demonstrated that overexpression of miR-15a/16 resulted in decreased TGF-beta3 signaling and VEGF levels in cultured REC grown in high glucose conditions. In addition, the levels of tight junction proteins, zonula occludens-1 (ZO-1) and occludin, were elevated in REC following overexpression of miR-15a and -16. Overexpression of miR-15a and - 16 played a role in reducing cellular permeability through inhibition of VEGF signaling in REC cultured under high glucose conditions. Using miR-15a-transgenic mice, we demonstrated the regulatory role of miR-15a on TGF-beta3 signaling and tight junction proteins in vivo. Our outcomes suggest that miR-15a/16 maintain the retinal endothelial cell barrier by reducing TGFbeta3/VEGF signaling and increasing levels of key tight junction proteins.

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Section: Discussionmentioning

confidence: 99%

miR-15a/16 inhibits TGF-beta3/VEGF signaling and increases retinal endothelial cell barrier proteins

Liu

Steinle

2017

Vision Research

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“…MicroRNAs (miRNAs) have demonstrable potential as diagnostic, predictive, and prognostic markers, and may provide a promising new class of therapeutic targets [15–17]. MiRNAs are small 17–25 nucleotide non-coding RNA molecules, which regulate post-transcriptional gene expression in a sequence-specific manner and have a central role in multiple biological functions, including cell survival, proliferation, and DNA damage responses [18–20].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the glucocorticoid receptor results in an enhanced miR-99a/100-mediated radiation response in stem-like cells from human prostate cancers

et al. 2016

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Radiation therapy is a major primary treatment option for both localized early stage prostate cancer, and for advanced, regionally un-resectable, cancer. However, around 30% of patients still experience biochemical recurrence after radiation therapy within 10 years. Thus, identification of better biomarkers and new targets are urgently required to improve current therapeutic strategies. The miR-99 family has been shown to play an important role in the regulation of the DNA damage response, via targeting of the SWI/SNF chromatin remodeling factors, SMARCA5 and SMARCD1 in cell line models. In the present study, we have demonstrated that low expression of miR-99a and miR-100 is present in cell populations which are relatively radiation insensitive, for example in prostate cancer stem cells and in castration-resistant prostate cancer. Additionally, treatment of cells with the synthetic glucocorticoid, Dexamethasone resulted in decreased miR-99a and 100 expression, suggesting a new mechanism of miR-99a and 100 regulation in androgen-independent prostate cells. Strikingly, treatment of prostate cells with the glucocorticoid receptor inhibitor, Mifepristone was found to sensitize prostate cells to radiation by increasing the levels of miR-99a and miR-100. These results qualify the miR99 family as markers of radiation sensitivity and as potential therapeutic targets to improve efficiency of radiotherapy.

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“…PC is challenging to treat due to its high metastasis rate (2); despite considerable advances in the treatment of PC, metastatic prostate cancer (MPC) remains incurable (3). The molecular mechanisms underlying the metastasis of PC cells remain largely unknown and require further study.…”

Section: Introductionmentioning

confidence: 99%

Comparison of miRNA and gene expression profiles between metastatic and primary prostate cancer

Guo

Zhu

et al. 2017

Oncol Lett

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Abstract. The present study aimed to identify the regulatory mechanisms associated with the metastasis of prostate cancer (PC). The microRNA (miRNA/miR) microarray dataset GSE21036 and gene transcript dataset GSE21034 were downloaded from the Gene Expression Omnibus database. Following pre-processing, differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) between samples from patients with primary prostate cancer (PPC) and metastatic prostate cancer (MPC) with |log 2 fold change (FC)| >1 and a false discovery rate <0.05 were selected using the Linear Models for Microarray and RNA-seq Data 4 package of R. Next, a DEM-DEG regulatory network was constructed by downloading miRNA-DEG pairs from the miRNA.org database. Finally, functional annotation of each DEM-DEG module was performed using the Database for Annotation, Visualization and Integrated Discovery based on the Gene Ontology database. The upregulated miRNAs, including miR-144, miR-494 and miR-181a, exhibited a higher degree of connections compared with other nodes, including in the DEM-DEG regulatory network, and regulated a number of downregulated DEGs. According to the functional annotation of the DEM-DEG modules, miR-144 and its targeted DEGs enriched the highest number of biological process terms (36 terms), followed by miR-494 (24 terms), miR-30d (18 terms), miR-181a (15 terms), hsa-miR-196a (8 terms), miR-708 (7 terms) and miR-486-5p (2 terms). Therefore, these miRNAs may serve roles in the metastasis of PC cells via downregulation of their corresponding target DEGs.

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A microRNA code for prostate cancer metastasis

Cited by 117 publications

References 66 publications

miR-15a/16 inhibits TGF-beta3/VEGF signaling and increases retinal endothelial cell barrier proteins

miR-15a/16 inhibits TGF-beta3/VEGF signaling and increases retinal endothelial cell barrier proteins

Inhibition of the glucocorticoid receptor results in an enhanced miR-99a/100-mediated radiation response in stem-like cells from human prostate cancers

Comparison of miRNA and gene expression profiles between metastatic and primary prostate cancer

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