miRNA-708 Control of CD44+ Prostate Cancer–Initiating Cells

Saini, Sharanjot; Majid, Shahana; Shahryari, Varahram; Arora, Sumit; Yamamura, Soichiro; Chang, Inik; Zaman, Mohd Saif; Deng, Guoren; Tanaka, Yuichiro; Dahiya, Rajvir

doi:10.1158/0008-5472.can-12-0540

Cited by 118 publications

(115 citation statements)

References 37 publications

(66 reference statements)

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“…Among the 130 miRNAs that showed high expression in our present study, 18 have already been linked to PCa relapse (11)(12)(13)(27)(28)(29)(30). Our results are in agreement with earlier reports that showed that miR-26b, miR-30a-3p, and miR-26a correlate with biochemical failure (12 ).…”

Section: Discussionsupporting

confidence: 93%

MicroRNA Signature Helps Distinguish Early from Late Biochemical Failure in Prostate Cancer

et al. 2013

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PURPOSE Prostate-specific antigen testing has led to overtreatment of prostate cancer (PCa). Only a small subset of PCa patients will have an aggressive disease that requires intensive therapy, and there is currently no biomarker to predict disease aggressiveness at the time of surgery. MicroRNAs (miRNAs) are reported to be involved in PCa pathogenesis. METHODS This study involved 105 participants. For the discovery phase, prostatectomy samples were dichotomized to high-risk (n = 27, biochemical failure <36 months after prostatectomy) and low-risk groups (n = 14, ≥36 months without biochemical failure). Expression of 754 mature miRNAs was compared between the 2 groups. Linear regression models were built to accurately predict biochemical failure risk. miRNA mimics were transfected into PCa model cell lines to test effects on proliferation and to deduce responding signaling pathways. RESULTS We identified 25 differentially expressed miRNAs between the biochemical failure risk groups. Based on the expression of 2–3 miRNAs, 3 logistic regression models were developed, each with a high positive predictive value. Candidate miRNAs and the best-performing model were also verified on an independent PCa set. miRNA-152, featured in the models, was further investigated by using cell line models and was shown to affect cell proliferation. Predicted interaction between miR-152 and (mRNA)ERBB3 (erythroblastic leukemia viral oncogene homolog 3) was experimentally validated in vitro. CONCLUSIONS miRNAs can help to predict biochemical failure risk at the time of prostatectomy.

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Section: Discussionsupporting

confidence: 93%

MicroRNA Signature Helps Distinguish Early from Late Biochemical Failure in Prostate Cancer

et al. 2013

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“…These aberrantly expressed miRNAs play essential roles in the regulation of TIC properties as either TIC suppressors or promoters [20][21][22][23][24] . Moreover, a series of critical signalling pathways involved in the regulation of TIC properties have been uncovered with the identification of the targets of these miRNAs 19,[25][26][27][28] . Importantly, miRNAs are also demonstrated to be promising biomarkers and amenable therapeutic targets 5,19,24 .…”

mentioning

confidence: 99%

PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

Han

Zhao

et al. 2015

Nat Commun

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Tumour-initiating cells (TICs) are advocated to constitute the sustaining force to maintain and renew fully established malignancy; however, the molecular mechanisms responsible for these properties are elusive. We previously demonstrated that voltage-gated calcium channel a2d1 subunit marks hepatocellular carcinoma (HCC) TICs. Here we confirm directly that a2d1 is a HCC TIC surface marker, and identify let-7c, miR-200b, miR-222 and miR-424 as suppressors of a2d1 þ HCC TICs. Interestingly, all the four miRNAs synergistically target PBX3, which is sufficient and necessary for the acquisition and maintenance of TIC properties. Moreover, PBX3 drives an essential transcriptional programme, activating the expression of genes critical for HCC TIC stemness including CACNA2D1, EpCAM, SOX2 and NOTCH3. In addition, the expression of CACNA2D1 and PBX3 mRNA is predictive of poor prognosis for HCC patients. Collectively, our study identifies an essential signalling pathway that controls the switch of HCC TIC phenotypes.

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“…Interestingly, bioinformatics approaches have predicted onethird of all mammalian genes to be targeted and regulated by miRNAs [25][26][27]. Previous studies have shown that aberrant miRNA expression could impact normal biological processes, resulting in PC initiation and progression [28][29][30]. However, a role of miR-323 in the carcinogenesis of PC has not been studied.…”

Section: Introductionmentioning

confidence: 99%

MiR-323 Inhibits Prostate Cancer Vascularization Through Adiponectin Receptor

Gao

Yao

Zheng

2015

Cell Physiol Biochem

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Background/Aims: The current treatments fail to provide satisfactory cure for aggressive prostate cancers (PCs). Hence, further comprehension of PC metastasis is highly appreciated for improving the levels of therapy. We have previously shown that Adiponectin reduces the levels of vascular endothelial growth factor A (VEGF-A) in PCs to suppress tumor-associated neovascularization, possibly through AMPK/mTor signaling. Here, we studied the regulation of Adiponectin signaling in PCs. Methods: We analyzed the levels and correlation of Adiponectin receptor 1 (AdipoR1) and microRNA-323 (miR-323) in the PC specimen, compared to the paired normal prostate tissue. We analyzed the binding of miR-323 to the 3'UTR of AdipoR1 mRNA and its effects on AdipoR1 translation by bioinformatics analysis and by luciferase-reporter assay, respectively. We modified miR-323 levels in PC cells, and examined the effects on the expression of AdipoR1 and VEGF-A, as well as on vessel formation in a human umbilical vein endothelial cells (HUVECs) transwell collagen gel assay. Results: We detected significantly lower levels of AdipoR1 and significantly higher levels of miR-323 in PC specimen. Moreover, the levels of AdipoR1 and miR-323 are inversely correlated. Moreover, miR-323 was found to bind to the 3'UTR of AdipoR1 mRNA to inhibit its translation. Overexpression of miR-323 in PC cells decreased AdipoR1 protein levels, whereas inhibition of miR-323 increased AdipoR1 protein levels, without affecting AdipoR1 transcripts. Moreover, overexpression of miR-323 increased the levels of VEGF-A and the vessel formation by HUVECs, while inhibition of miR-323 decreased the levels of VEGF-A and the vessel formation by HUVECs. Conclusion: Our data demonstrate that miR-323 may increase VEGF-A-mediated cancer vascularization in PC cells through AdipoR1 suppression.

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miRNA-708 Control of CD44+ Prostate Cancer–Initiating Cells

Abstract: Tumor recurrence in prostate cancer has been attributed to the presence of CD44-expressing tumorinitiating cells. In this study, we report that miR-708 is a key negative regulator of this CD44

Cited by 118 publications

References 37 publications

MicroRNA Signature Helps Distinguish Early from Late Biochemical Failure in Prostate Cancer

MicroRNA Signature Helps Distinguish Early from Late Biochemical Failure in Prostate Cancer

PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

MiR-323 Inhibits Prostate Cancer Vascularization Through Adiponectin Receptor

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