FOXP3–miR-146–NF-κB Axis and Therapy for Precancerous Lesions in Prostate

Liu, Runhua; Yi, Bin; Wei, Shi; Yang, Wei‐Hsiung; Hart, Karen; Chauhan, Priyanka; Zhang, Wei; Mao, Xiaoyu; Liu, Xiuping; Liu, Chang Gong; Wang, Lizhong

doi:10.1158/0008-5472.can-14-2109

Cited by 43 publications

(56 citation statements)

References 45 publications

(78 reference statements)

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“…Frozen tissue sections were used for laser capture microdissection to obtain prostate epithelial and cancer cells, as described previously (30, 31). For analysis of gene expression, 5000 cells were microdissected from target tissues.…”

Section: Methodsmentioning

confidence: 99%

“…Western blotting was performed as described previously (6, 31). WT or mutant p53-transfected PC3 cells were used for ChIP assays, as described previously (6, 31).…”

Section: Methodsmentioning

confidence: 99%

“…WT or mutant p53-transfected PC3 cells were used for ChIP assays, as described previously (6, 31). Briefly, cells were sonicated and fixed with 1% paraformaldehyde.…”

Section: Methodsmentioning

confidence: 99%

“…After 2 weeks, mice were treated every other day with intraperitoneal injections of 100 μL of PRIMA-1 (100 mg/kg) or PBS for 2 weeks. Tumor size and weight were measured as described previously (30, 31). …”

Section: Methodsmentioning

confidence: 99%

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Silencing of CD24 Enhances the PRIMA-1–Induced Restoration of Mutant p53 in Prostate Cancer Cells

Zhang

Wang

et al. 2016

Clinical Cancer Research

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Purpose: In prostate cancer cells, there is CD24-dependent inactivation of mutant p53, but the mechanism and its significance remain largely unknown. Here, we validated this observation and explored the therapeutic potential of targeting CD24 in TP53 mutant prostate cancer cells.Experimental Design: Overall, 553 prostate cancers (522 formalin-fixed paraffin-embedded and 31 frozen tissues) were assessed for protein or mRNA expression of CD24 and TP53. The effects of CD24 on p53-dependent transcriptional regulation, cancer cell growth, the cell cycle, apoptosis, and mutant p53 restoration were also determined.Results: As determined with three sample cohorts, CD24 and p53 were not expressed in prostate epithelial cells but in prostate cancer cells in 48% of cases for CD24 and 16% of cases for p53 (mutant form). Expressions of CD24 and mutant p53 were more frequently observed in late-stage and metastatic prostate tumors. Mutant p53 accompanied with CD24 was expressed in most cases (91.6%, 76/83). Silencing of CD24 increased the transcriptional activity of p53 target genes, such as CDKNA1, VDR, and TP53INP1, leading to suppression of p53-dependent cell growth, cell-cycle arrest, and apoptosis in most TP53-mutant prostate cancer cells. Silencing of CD24 enhanced restoration of PRIMA-1-induced mutant p53 in endogenous TP53 P223L/V274F DU145 cells and in PC3 cells transfected with TP53 R273H . Conclusions: In human prostate cancers, there is CD24-dependent inactivation of mutant p53. The coexpression of CD24 and p53 may help identify aggressive cancers. Targeting CD24 provides a strategy to enhance mutant p53-restoring therapies, especially in patients with TP53 R273H prostate cancer.

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Section: Methodsmentioning

confidence: 99%

“…Western blotting was performed as described previously (6, 31). WT or mutant p53-transfected PC3 cells were used for ChIP assays, as described previously (6, 31).…”

Section: Methodsmentioning

confidence: 99%

“…WT or mutant p53-transfected PC3 cells were used for ChIP assays, as described previously (6, 31). Briefly, cells were sonicated and fixed with 1% paraformaldehyde.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Silencing of CD24 Enhances the PRIMA-1–Induced Restoration of Mutant p53 in Prostate Cancer Cells

Zhang

Wang

et al. 2016

Clinical Cancer Research

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“…Previously published studies explained that the excessive expression of miR-146a influenced the PCa cells in terms of apoptosis, progression, and viability by directly targeting the epidermal growth factor receptor (EGFR) (5), Ras-related C3 botulinum toxin substrate 1 (Rac1) (6), ROCK1 (7), interleukin-1 receptor-associated kinase 1 (IRAK1), and tumor necrosis factor receptor-associated factor 6 (TRAF6) (8). Although miR-146a acts as a tumor suppressor in PCa cells, current knowledge on the molecular mechanisms that contribute to the expression of miR-146a in PCa cells is still limited.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of miR-146a by YY1 depletion correlates with delayed progression of prostate cancer

Huang

Tao

Liu

et al. 2017

International Journal of Oncology

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Previously published studies explained that the excessive expression of miR-146a influences the prostate cancer (PCa) cells in terms of apoptosis, progression, and viability. Although miR-146a acts as a tumor suppressor, current knowledge on the molecular mechanisms that controls its expression in PCa is limited. In this study, gene set enrichment analysis (GSEA) showed negatively enriched expression of miR-146a target gene sets and positively enriched expression of gene sets suppressed by the enhancer of zeste homolog 2 (EZH2) after YY1 depletion in PCa cells. The current results demonstrated that the miR-146a levels in PCa tissues with high Gleason scores (>7) are significantly lower than those in PCa tissues with low Gleason scores (≤7), which were initially observed in the clinical specimens. An inverse relationship between YY1 and miR-146a expression was also observed. Experiments indicated the decrease in cell viability, proliferation, and promoting apoptosis after YY1 depletion, while through inhibiting miR-146a could alleviate the negative effect brought by YY1 depletion. We detected the reversed adjustment of YY1 to accommodate miR-146a transcriptions. On the basis of YY1 depletion, we determined that the expression of miR-146a increased after EZH2 knockdown. We validated the combination of YY1 and its interaction with EZH2 at the miR-146a promoter binding site, thereby prohibiting the transcriptional activity of miR-146a in PCa cells. Our results suggested that YY1 depletion repressed PCa cell viability and proliferation and induced apoptosis at least in a miR-146a-assisted manner.

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Defining fallopian tube‐derived miRNA cancer signatures

Dejene

Öhman

et al. 2019

Cancer Medicine

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BackgroundMicroRNAs have recently emerged as promising circulating biomarkers in diverse cancer types, including ovarian cancer. We utilized conditional, doxycycline‐induced fallopian tube (FT)‐derived cancer models to identify changes in miRNA expression in tumors and plasma, and further validated the murine findings in high‐grade ovarian cancer patient samples.MethodsWe analyzed 566 biologically informative miRNAs in doxycycline‐induced FT and metastatic tumors as well as plasma samples derived from murine models bearing inactivation of Brca, Tp53, and Pten genes. We identified miRNAs that showed a consistent pattern of dysregulated expression and validated our results in human patient serum samples.ResultsWe identified six miRNAs that were significantly dysregulated in doxycycline‐induced FTs (P < .05) and 130 miRNAs differentially regulated in metastases compared to normal fallopian tissues (P < .05). Furthermore, we validated miR‐21a‐5p, miR‐146a‐5p, and miR‐126a‐3p as dysregulated in both murine doxycycline‐induced FT and metastatic tumors, as well as in murine plasma and patient serum samples.ConclusionsIn summary, we identified changes in miRNA expression that potentially accompany tumor development in murine models driven by commonly found genetic alterations in cancer patients. Further studies are required to test both the function of these miRNAs in driving the disease and their utility as potential biomarkers for diagnosis and/or disease progression.

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FOXP3–miR-146–NF-κB Axis and Therapy for Precancerous Lesions in Prostate

Cited by 43 publications

References 45 publications

Silencing of CD24 Enhances the PRIMA-1–Induced Restoration of Mutant p53 in Prostate Cancer Cells

Silencing of CD24 Enhances the PRIMA-1–Induced Restoration of Mutant p53 in Prostate Cancer Cells

Upregulation of miR-146a by YY1 depletion correlates with delayed progression of prostate cancer

Defining fallopian tube‐derived miRNA cancer signatures

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