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

Huang, Yeqing; Tao, Tao; Liu, Chunhui; Guan, Han; Zhang, Guangyuan; Ling, Zhixin; Zhang, Lei; Lǚ, Kai; Chen, Shuqiu; Xu, Bin; Chen, Ming

doi:10.3892/ijo.2017.3840

Cited by 20 publications

(16 citation statements)

References 33 publications

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“…However, as mentioned above, YY1 also represses miR-186 and hence might promote prostate tumorigenesis. Likewise, an inverse correlation in the expression of YY1 and miR-146a has been reported in prostate cancer (111) as explained above.…”

Section: Prostate Cancermentioning

confidence: 52%

“…It was shown that YY1 binds to XAF1 promoter and thereby inhibits its expression in prostate cancer cell lines in a HDAC1 dependent mechanism (91). In addition to repression of regular genes, YY1 has also been shown to repress tumor suppressive miR-146a in prostate cancer cells upon interacting with EZH2 and thereby promotes prostate tumor growth (111). Further, YY1 also contributes to the metastatic potential of the prostate cancer cells by mediating transcriptional repression of heterogeneous nuclear ribonucleoprotein M (hnRNPM), which is an inhibitor of migration and invasion of prostate cancer cells (132).…”

Section: Prostate Cancermentioning

confidence: 99%

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The Two Sides of YY1 in Cancer: A Friend and a Foe

2019

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Yin Yang 1 (YY1), a dual function transcription factor, is known to regulate transcriptional activation and repression of many genes associated with multiple cellular processes including cellular differentiation, DNA repair, autophagy, cell survival vs. apoptosis, and cell division. Owing to its role in processes that upon deregulation are linked to malignant transformation, YY1 has been implicated as a major driver of many cancers. While a large body of evidence supports the role of YY1 as a tumor promoter, recent reports indicated that YY1 also functions as a tumor suppressor. The mechanism by which YY1 brings out opposing outcome in tumor growth vs. suppression is not completely clear and some of the recent reports have provided significant insight into this. Likewise, the mechanism by which YY1 functions both as a transcriptional activator and repressor is not completely clear. It is likely that the proteins with which YY1 interacts might determine its function as an activator or repressor of transcription as well as its role as a tumor suppressor or promoter. Hence, a collection of YY1-protein interactions in the context of different cancers would help us gain an insight into how YY1 promotes or suppresses cancers. This review focuses on the YY1 interacting partners and its target genes in different cancer models. Finally, we discuss the possibility of therapeutically targeting the YY1 in cancers where it functions as a tumor promoter.

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Section: Prostate Cancermentioning

confidence: 52%

Section: Prostate Cancermentioning

confidence: 99%

The Two Sides of YY1 in Cancer: A Friend and a Foe

2019

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“…Similarly, the top five most upregulated miRNAs in APC were miR-375, miR-26a-5p, miR-142-3p, miR-451a, and miR-215-5p, which were also upregulated in APC relative to LPC (Table 2). Thus, in addition to identifying several novel dysregulated miRNAs in plasma samples from PC patients, we were able to confirm a significant upregulation of the established PC-associated oncomir miR-375 [32][33][34][35], and a significant downregulation of the tumor suppressor miR-146a-5p [36][37][38].…”

Section: Dysregulated Mirnas In Plasmamentioning

confidence: 69%

Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Fredsøe

Rasmussen²,

Mouritzen³

et al. 2020

Diagnostics

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Early detection of prostate cancer (PC) is paramount as localized disease is generally curable, while metastatic PC is generally incurable. There is a need for improved, minimally invasive biomarkers as current diagnostic tools are inaccurate, leading to extensive overtreatment while still missing some clinically significant cancers. Consequently, we profiled the expression levels of 92 selected microRNAs by RT-qPCR in plasma samples from 753 patients, representing multiple stages of PC and non-cancer controls. First, we compared plasma miRNA levels in patients with benign prostatic hyperplasia (BPH) or localized prostate cancer (LPC), versus advanced prostate cancer (APC). We identified several dysregulated microRNAs with a large overlap of 59 up/down-regulated microRNAs between BPH versus APC and LPC versus APC. Besides identifying several novel PC-associated dysregulated microRNAs in plasma, we confirmed the previously reported upregulation of miR-375 and downregulation of miR-146a-5p. Next, by randomly splitting our dataset into a training and test set, we identified and successfully validated a novel four microRNA diagnostic ratio model, termed bCaP (miR-375*miR-33a-5p/miR-16-5p*miR-409-3p). Combined in a model with prostate specific antigen (PSA), digital rectal examination status, and age, bCaP predicted the outcomes of transrectal ultrasound (TRUS)-guided biopsies (negative vs. positive) with greater accuracy than PSA alone (Training: area under the curve (AUC), model = 0.84; AUC, PSA = 0.63. Test set: AUC, model = 0.67; AUC, PSA = 0.56). It may be possible in the future to use this simple and minimally invasive bCaP test in combination with existing clinical parameters for a more accurate selection of patients for prostate biopsy.

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“…IHC was performed using anti-EZH2 antibody (1:250, Abcam, Cambrige, MA, USA) according to the manufacturer’s instructions. The original magnification: ×200.The specific evaluation of gene expression via ISH or IHC was calculated as previously described [ 30 ]. In brief, sections with no labeling or less than 5% labeled cells were scored as 0, 5%–30% of cells as 1, 31%–70% of cells as 2, and ≥71% as 3.…”

Section: Methodsmentioning

confidence: 99%

“…A combined score of 0–1 indicates negative expression (−), 2–3 indicates weak expression (+), 4–5 indicated moderate expression (++), and 6 indicates strong expression (+++). Each sample was examined separately and scored by two pathologists [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

Involvement of aberrantly activated HOTAIR/EZH2/miR-193a feedback loop in progression of prostate cancer

Ling

Wang

Tao

et al. 2017

J Exp Clin Cancer Res

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BackgroundThough androgen deprivation therapy is the standard treatment for prostate cancer (PCa), most patients would inevitably progress to castration-resistant prostate cancer (CRPC) which is the main cause of PCa death. Therefore, the identification of novel molecular mechanism regulating cancer progression and achievement of new insight into target therapy would be necessary for improving the benefits of PCa patients. This study aims to study the function and regulatory mechanism of HOTAIR/EZH2/miR-193a feedback loop in PCa progression.MethodsMSKCC and TCGA datasets were used to identify miR-193a expression profile in PCa. Cell Counting Kit-8 (CCK-8) assays, colony formation, invasion, migration, flow cytometry, a xenograft model and Gene Set Enrichment Analysis were used to detect and analyze the biological function of miR-193a. Then, we assessed the role of HOTAIR and EZH2 in regulation of miR-193a expression by using plasmid, lentivirus and small interfering RNA (siRNA). Luciferase reporter assays and chromatin immunoprecipitation assays were performed to detect the transcriptional activation of miR-193a by EZH2 and HOTAIR. Further, qRT-PCR and luciferase reporter assays were conducted to examine the regulatory role of miR-193a controlling the HOTAIR expression in PCa. Finally, the correlation between HOTAIR, EZH2 and miR-193a expression were analyzed using In situ hybridization and immunohistochemistry.ResultsWe found that miR-193a was significantly downregulated in metastatic PCa through mining MSKCC and TCGA datasets. In vitro studies revealed that miR-193a inhibited PCa cell growth, suppressed migration and invasion, and promoted apoptosis; in vivo results demonstrated that overexpression of miR-193a mediated by lentivirus dramatically reduced PCa xenograft tumor growth. Importantly, we found EZH2 coupled with HOTAIR to repress miR-193a expression through trimethylation of H3K27 at miR-193a promoter in PC3 and DU145 cells. Interestingly, further evidence illustrated that miR-193a directly targets HOTAIR showing as significantly reduced HOTAIR level in miR-193a overexpressed cells and tissues. The expression level of miR-193a was inversely associated with that of HOTAIR and EZH2 in PCa.ConclusionThis study firstly demonstrated that miR-193a acted as tumor suppressor in CRPC and the autoregulatory feedback loop of HOTAIR/EZH2/miR-193a served an important mechanism in PCa development. Targeting this aberrantly activated feedback loop may provide a potential therapeutic strategy.Electronic supplementary materialThe online version of this article (doi: 10.1186/s13046-017-0629-7) contains supplementary material, which is available to authorized users.

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

Cited by 20 publications

References 33 publications

The Two Sides of YY1 in Cancer: A Friend and a Foe

The Two Sides of YY1 in Cancer: A Friend and a Foe

Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Involvement of aberrantly activated HOTAIR/EZH2/miR-193a feedback loop in progression of prostate cancer

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