The miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts

Dambal, Shweta; Baumann, Bethany; McCray, Tara; Williams, La Tanya; Richards, Zachary; Deaton, Ryan; Prins, Gail S.; Nonn, Larisa

doi:10.1038/s41598-017-07979-y

Cited by 18 publications

(19 citation statements)

References 55 publications

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“…The mechanism of stabilization could be explained by involving the amino groups of chitosan in the binding of zinc ions as well as ionic cross-linking with TPP molecules [ 76 ]. Although zinc is not used as a direct decoy for tumors in nanopharmaceuticals, several studies have pointed out the enhanced uptake of zinc ions in prostate cancer [ 80 , 81 ]. Normal prostate glands contain higher levels of zinc compared with cancerous tissues as well as the levels of MT.…”

Section: Discussionmentioning

confidence: 99%

Zinc-Modified Nanotransporter of Doxorubicin for Targeted Prostate Cancer Delivery

et al. 2017

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This work investigated the preparation of chitosan nanoparticles used as carriers for doxorubicin for targeted cancer delivery. Prepared nanocarriers were stabilized and functionalized via zinc ions incorporated into the chitosan nanoparticle backbone. We took the advantage of high expression of sarcosine in the prostate cancer cells. The prostate cancer targeting was mediated by the AntiSar antibodies decorated surface of the nanocage. Formation of the chitosan nanoparticles was determined using a ninhydrin assay and differential pulse voltammetry. Obtained results showed the strong effect of tripolyphosphine on the nanoparticle formation. The zinc ions affected strong chitosan backbone coiling both in inner and outer chitosan nanoparticle structure. Zinc electrochemical signal depended on the level of the complex formation and the potential shift from −960 to −950 mV. Formed complex is suitable for doxorubicin delivery. It was observed the 20% entrapment efficiency of doxorubicin and strong dependence of drug release after 120 min in the blood environment. The functionality of the designed nanotransporter was proven. The purposed determination showed linear dependence in the concentration range of Anti-sarcosine IgG labeled gold nanoparticles from 0 to 1000 µg/mL and the regression equation was found to be y = 3.8x − 66.7 and R2 = 0.99. Performed ELISA confirmed the ability of Anti-sarcosine IgG labeled chitosan nanoparticles with loaded doxorubicin to bind to the sarcosine molecule. Observed hemolytic activity of the nanotransporter was 40%. Inhibition activity of our proposed nanotransporter was evaluated to be 0% on the experimental model of S. cerevisiae. Anti-sarcosine IgG labeled chitosan nanoparticles, with loaded doxorubicin stabilized by Zn ions, are a perspective type of nanocarrier for targeted drug therapy managed by specific interaction with sarcosine and metallothionein for prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Zinc-Modified Nanotransporter of Doxorubicin for Targeted Prostate Cancer Delivery

et al. 2017

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“…To further elucidate the regulatory mechanism of Erbin in AML, a bioinformatics method was employed to predict and screen the possible targets of Erbin, and miR-183-5p was found to bind directly to the 3′ UTR of Erbin. The function of miR-183 in tumors has been intensively reported; it often shows high expression in tumors, accompanied by allelic imbalance, chromosome breakage, and increased copy number, 11 , 12 , 13 , 14 , 15 , 16 , 17 and most of these phenotypes are manifested as carcinogenic. Some phenotypes also show tumor suppressor activity, suggesting that its tumorigenicity may be dependent on the environment and cell type.…”

Section: Discussionmentioning

confidence: 99%

miR-183-5p Inhibits Occurrence and Progression of Acute Myeloid Leukemia via Targeting Erbin

Zheng

Zhu

et al. 2019

Molecular Therapy

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Erbin has been shown to have significant effects on the development of solid tumors. However, little is known about its function and regulatory mechanism in hematological malignancies. The biological function of Erbin on cell proliferation was measured in vitro and in vivo. The predicted target of Erbin was validated by dual-luciferase reporter assay and rescue experiment. We found that overexpression of Erbin could inhibit the cell proliferation and promote the cell differentiation of acute myeloid leukemia (AML) cells, whereas depletion of Erbin could enhance the cell proliferation and block the cell differentiation in AML cells in vitro and in vivo. Besides, miR-183-5p was identified as the upstream regulator that negatively regulated the Erbin expression. The results were confirmed by dual-luciferase reporter and RNA pull-down assay. Furthermore, we found that miR-183-5p negatively regulated Erbin, resulting in enhanced cell proliferation of AML cells via activation of RAS/RAF/MEK/ERK and PI3K/AKT/FoxO3a pathways. The activation of RAS/RAF/MEK/ERK and PI3K/AKT/ FoxO3a pathways was mediated by Erbin interacting with Grb2. These results were also validated by rescue experiments in vitro and in vivo. All above-mentioned findings indicated that the miR-183-5p/Erbin signaling pathway might represent a novel prognostic biomarker or therapeutic target for treatment of AML.

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“…Ueno reported that miR-183 could target Dkk-3 and SAMAD4 and has an oncogenic biological behavior [ 17 ]. Due to the paralogous property of miR-183, miR-96, and miR-182, these three miRNAs have been studied as miR-183 cluster, which could regulate zinc levels and carcinogenic pathways in prostate cells [ 18 ]. MiR-96 was also reported enhancing PCa cell proliferation through FOXO1 [ 19 ], which could be speculated in the PPI network ( Figure 2(a) ).…”

Section: Discussionmentioning

confidence: 99%

Identification of the Key MicroRNAs and the miRNA-mRNA Regulatory Pathways in Prostate Cancer by Bioinformatics Methods

Hao

Song

2018

BioMed Research International

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Objective To identify key microRNAs (miRNAs) and their regulatory networks in prostate cancer. Methods Four miRNA and three gene expression microarray datasets were downloaded for analysis from Gene Expression Omnibus database. The differentially expressed miRNA and genes were accessed by a GEO2R. Functional and pathway enrichment analyses were performed using the DAVID program. Protein-protein interaction (PPI) and miRNA-mRNA regulatory networks were constructed using the STRING and Cytoscape tool. Moreover, the results and clinical significance were validated in TCGA data. Results We identified 26 significant DEMs, 633 upregulated DEGs, and 261 downregulated DEGs. Functional enrichment analysis indicated that significant DEGs were related to TGF-beta signaling pathway and TNF signaling pathway in PCa. Key DEGs such as HSPA8, PPP2R1A, CTNNB1, ADCY5, ANXA1, and COL9A2 were found as hub genes in PPI networks. TCGA data supported our results and the miRNAs were correlated with clinical stages and overall survival. Conclusions We identified 26 miRNAs that may take part in key pathways like TGF-beta and TNF pathways in prostate cancer regulatory networks. MicroRNAs like miR-23b, miR-95, miR-143, and miR-183 can be utilized in assisting the diagnosis and prognosis of prostate cancer as biomarkers. Further experimental studies are required to validate our results.

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The miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts

Cited by 18 publications

References 55 publications

Zinc-Modified Nanotransporter of Doxorubicin for Targeted Prostate Cancer Delivery

Zinc-Modified Nanotransporter of Doxorubicin for Targeted Prostate Cancer Delivery

miR-183-5p Inhibits Occurrence and Progression of Acute Myeloid Leukemia via Targeting Erbin

Identification of the Key MicroRNAs and the miRNA-mRNA Regulatory Pathways in Prostate Cancer by Bioinformatics Methods

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