Widespread deregulation of microRNA expression in human prostate cancer

Özen, Mustafa; Creighton, Chad J.; Ozdemir, Merve Erkinay; Ittmann, Michael

doi:10.1038/sj.onc.1210809

Cited by 585 publications

(543 citation statements)

References 21 publications

(34 reference statements)

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“…Tong et al 12 investigated the association between the miRNA expression profile and clinical data using 40 prostatectomy specimens, although the sample size was smaller than that of Schaefer et al 2 and our study. 2,12 They found five downregulated types of miRNA, including miR-145, and emphasized that the finding of decreased miR-145 expression was consistent with the finding that miR-145 was one of the most frequently downregulated types of miRNA in 16 prostatectomy specimens in the study by Ozen et al 10 Decreased miR-145 expression has been described in lung caner, breast cancer and hepatocellular carcinoma. 17,18 In addition, the expression of miR-145 has consistently been found to be decreased in the adenomatous and cancer stages of colorectal cancer.…”

Section: Discussionsupporting

confidence: 58%

“…19,20 Porkka et al 11 reported that miR-145 was downregulated in PCa compared with BPH. Ozen et al 10 also reported that miR-145 was significantly downregulated in prostate cancer as determined by miRNA microarrays. However, we did not find an association between the expression of miRNA-145 and clinicopathologic parameters in prostate cancer.…”

Section: Discussionmentioning

confidence: 95%

“…In other words, a tumor tissue sample may include normal or benign prostate hyperplasia tissue even though a microdissection was performed to include over 90% of the tumor based on H&E stain preparation. 10,11 In our study, we also tried to include over 90% of the tumor through H&E stain preparation.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8] However, to date, few articles have investigated miRNA regulation in prostate cancer and only five studies have examined miRNA expression in more than 10 samples, with highly inconsistent results. 2,[9][10][11][12][13] Schaefer et al 4 reported that there is no overlapping subset between the down-and upregulated miRNA patterns of previous studies. In addition, 17 of the 105 types of miRNA even showed an opposite expression pattern.…”

Section: Introductionmentioning

confidence: 97%

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Do microRNA 96, 145 and 221 expressions really aid in the prognosis of prostate carcinoma?

Kang

Ha²,

Kim³

et al. 2012

Asian J Androl

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MicroRNAs (miRs) are small noncoding RNAs that have been reported to be promising diagnostic tools. We used quantitative real-time reverse transcription PCR (RT-qPCR) to analyze differentially expressed miRNAs in prostate tumor samples to determine its prognostic value. From 2007 to 2009, tumor tissues were obtained from 73 radical prostatectomy specimens. Differentially expressed miR-96, -145 and -221 were validated by TaqMan RT-qPCR using all 73 tissues. The prognostic value was assessed in terms of biochemical recurrence using Kaplan-Meier and Cox regression analyses. For our patient cohort, the mean age was 64.7 years (50-76 years) and the mean prostate-specific antigen (PSA) was 7.5 ng ml 21 . During the follow-up period (mean, 19.4 months), 14 of 73 (19.2%) patients developed biochemical recurrence. Expression of miR-96, -145 and -221 correlated strongly with each other, but there were no correlations between miRNA expression and clinicopathologic parameters. Kaplan-Meier survival curves using the log-rank test showed a decreased biochemical recurrence-free interval with pathologic stage (P,0.001). In addition, patients with Gleason scores over 8, compared with those with a Gleason score of 6, showed a decreased biochemical recurrence-free interval in Kaplan-Meier analysis (P50.001). However, expression of miR-96, -145 and -221 did not correlate with the biochemical recurrence interval in Kaplan-Meier survival curves or by multivariate analysis using the Cox proportional hazard regression model, either. In conclusion, we did not observe a significant correlation between the expression of miR-96, -145 and -221 and clinicopathologic parameters. To utilize miRNA as a diagnostic tool in clinical practice, more research is needed to understand miRNA mechanisms, identify miRNA targets, and further characterize miRNA function.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

Do microRNA 96, 145 and 221 expressions really aid in the prognosis of prostate carcinoma?

Kang

Ha²,

Kim³

et al. 2012

Asian J Androl

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“…miR-125b is upregulated in prostate cancer and confirmed increased expression of one of these targets, EIF4EBP1, in prostate cancer tissues. 21 In terms of the analysis of miR-148a, three microarray data revealed that miR-148a was upregulated in clinical prostate tumors as compared with normal prostate tissues 13 and abundantly expressed in some AR-positive prostate cancer cell lines, such as LAPC4, LNCaP, and VCaP. 13,22 Our data provide the first evidence that miR-148a exhibits an androgen-inducible miR-148a promotes prostate cancer cell growth T Murata et al expression pattern in LNCaP cells.…”

Section: Discussionmentioning

confidence: 71%

miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression

Murata

Takayama

Katayama

et al. 2010

Prostate Cancer Prostatic Dis

132

105

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Recent advances in cancer biology reveal that microRNAs (miRNAs) are involved in the regulation of cancer-related genes, or they function as tumor suppressors or oncogenes. In prostate cancer, evidence has accumulated for the contribution of the androgen-dependent gene network to tumor growth, although the precise functions of miRNAs in prostate cancer remain to be investigated. Here, we identified androgen-responsive miRNAs by the short RNA sequencing analysis in LNCaP prostate cancer cells. Among 10 miRNAs with known sequences, we have determined that miR148a reduces the expression of cullin-associated and neddylation-dissociated 1 (CAND1), a negative regulator of SKP1-Cullin1-F-box (SCF) ubiquitin ligases, by binding to the 3 0 -untranslated region of CAND1 mRNA. CAND1 knockdown by small interfering RNA promoted the proliferation of LNCaP cells. Our study indicates the potential contribution of miR-148a to the growth of human prostate cancer.

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Methylation‐associated miR‐193b silencing activates master drivers of aggressive prostate cancer

et al. 2019

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Epigenetic silencing of miRNA is a primary mechanism of aberrant miRNA expression in cancer, and hypermethylation of miRNA promoters has been reported to contribute to prostate cancer initiation and progression. Recent data have shown that the miR‐193b promoter is hypermethylated in prostate cancer compared with normal tissue, but studies assessing its functional significance have not been performed. We aimed to elucidate the function of miR‐193b and identify its critical targets in prostate cancer. We observed an inverse correlation between miR‐193b level and methylation of its promoter in The Cancer Genome Atlas (TCGA) cohort. Overexpression of miR‐193b in prostate cancer cell lines inhibited invasion and induced apoptosis. We found that a majority of the top 150 genes downregulated when miR‐193b was overexpressed in liposarcoma are overexpressed in metastatic prostate cancer and that 41 miR‐193b target genes overlapped with the 86 genes in the aggressive prostate cancer subtype 1 (PCS1) signature. Overexpression of miR‐193b led to the inhibition of the majority of the 41 genes in prostate cancer cell lines. High expression of the 41 genes was correlated with recurrence of prostate cancer. Knockdown of miR‐193b targets FOXM1 and RRM2 in prostate cancer cells phenocopied overexpression of miR‐193b. Dual treatment with DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors decreased miR‐193b promoter methylation and restored inhibition of FOXM1 and RRM2 . Our data suggest that silencing of miR‐193b through promoter methylation may release the inhibition of PCS1 genes, contributing to prostate cancer progression and suggesting a possible therapeutic strategy for aggressive prostate cancer.

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Widespread deregulation of microRNA expression in human prostate cancer

Cited by 585 publications

References 21 publications

Do microRNA 96, 145 and 221 expressions really aid in the prognosis of prostate carcinoma?

Do microRNA 96, 145 and 221 expressions really aid in the prognosis of prostate carcinoma?

miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression

Methylation‐associated miR‐193b silencing activates master drivers of aggressive prostate cancer

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