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Project description:Yin Yang 1 regulates ITGAV and ITGB1, contributing to better prognosis of colorectal cancer
| PRJNA799233 | ENA
Project description:The Yin-Yang haplotype is defined as two mismatched haplotypes (Yin and Yang) representing the majority of the existing haplotypes in a particular genomic region. The human adenomatous polyposis coli (APC) gene shows a Yin-Yang haplotype pattern accounting for 84% of all of the haplotypes existing in the Spanish population. Several association studies have been published regarding APC gene variants (SNPs and haplotypes) and colorectal cancer (CRC) risk. However, no studies concerning diplotype structure and CRC risk have been conducted. The aim of the present study was to investigate whether the APC Yin-Yang homozygote diplotype is over-represented in patients with sporadic CRC when compared to its distribution in controls, and its association with CRC risk. TaqMan(®) assays were used to genotype three tagSNPs selected across the APC Yin-Yang region. Frequencies of the APC Yin-Yang tagSNP alleles, haplotype and diplotype of 378 CRC cases and 642 controls were compared. Two Spanish CRC group samples were included [Hospital Clínico San Carlos in Madrid (HCSC) and Instituto Catalán de Oncología in Barcelona (ICO)]. Analysis of 157 consecutive CRC patients and 405 control subjects from HCSC showed a significative effect for the risk of CRC (OR=1.93; 95% CI 1.32-2.81; P=0.001). However, this effect was not confirmed in 221 CRC patients and 237 control subjects from ICO (OR=0.89; 95% CI 0.61-1.28; P=0.521). We found a significant association between the APC homozygote Yin-Yang diplotype and the risk of colorectal cancer in the HCSC samples. However, we did not observe this association in the ICO samples. These observations suggest that a study with a larger Spanish cohort is necessary to confirm the effects of the APC Yin-Yang diplotype on the risk of CRC.
| S-EPMC3445875 | biostudies-literature
Project description:Many studies have established gene expression-based prognostic signatures for lung cancer. All of these signatures were built from training data sets by learning the correlation of gene expression with the patients' survival time. They require all new sample data to be normalized to the training data, ultimately resulting in common problems of low reproducibility and impracticality. To overcome these problems, we propose a new signature model which does not involve data training. We hypothesize that the imbalance of two opposing effects in lung cancer cells, represented by Yin and Yang genes, determines a patient's prognosis. We selected the Yin and Yang genes by comparing expression data from normal lung and lung cancer tissue samples using both unsupervised clustering and pathways analyses. We calculated the Yin and Yang gene expression mean ratio (YMR) as patient risk scores. Thirty-one Yin and thirty-two Yang genes were identified and selected for the signature development. In normal lung tissues, the YMR is less than 1.0; in lung cancer cases, the YMR is greater than 1.0. The YMR was tested for lung cancer prognosis prediction in four independent data sets and it significantly stratified patients into high- and low-risk survival groups (p?=?0.02, HR?=?2.72; p?=?0.01, HR?=?2.70; p?=?0.007, HR?=?2.73; p?=?0.005, HR?=?2.63). It also showed prediction of the chemotherapy outcomes for stage II & III. In multivariate analysis, the YMR risk factor was more successful at predicting clinical outcomes than other commonly used clinical factors, with the exception of tumor stage. The YMR can be measured in an individual patient in the clinic independent of gene expression platform. This study provided a novel insight into the biology of lung cancer and shed light on the clinical applicability.
| S-EPMC3714286 | biostudies-literature
Project description:BackgroundYin Yang-1 (YY1) is identified as a transcription factor with multiple functions. However, the role of YY1 in tumorigenesis remains controversial and its regulatory effects may depend upon not only cancer types, but also its interacting partners, chromatin structure, and the context in which it acts. It has been detected that YY1 was highly expressed in colorectal cancer (CRC). Intriguingly, many YY1-repressed genes exhibit tumor suppressive potential while YY1 silencing is related to chemotherapy resistance. Therefore, it is crucial to meticulously explore YY1 protein structure and the dynamic alteration of its interactome in each cancer type. This review attempts to describe the structure of YY1, summarize the mechanism that influence the expression level of YY1 and also highlight the recent advances in our understanding of regulatory insights of YY1 functions in CRC.MethodsRelated studies were identified through scoping search of PubMed, Web of science, Scopus and Emhase concerning the terms of "colorectal cancer", colorectal carcinoma" or CRC with "YY1". The retrieval strategy included title, abstract, and keywords with no language limitations. All the included articles were categorized depending on the mechanisms they explored.ResultsIn total, 170 articles were identified for further screening. After removing the duplication, not relevant outcomes and review articles, 34 were finally included in the review. Among them, 10 articles revealed the reasons of YY1 high expression in CRC, 13 articles explored YY1 function in CRC, and 11 articles fell into both aspects. In addition, we also summarized 10 clinical trials concerning the expression and activity of YY1 in various diseases, which offers a hint for future application.ConclusionsYY1 is highly expressed in CRC and broadly recognized as an oncogenic factor during the whole course of CRC. Sporadic controversial views are raised in term of CRC treatment, reminding us that future studies should take the influence of therapeutic regimens into concern.
| S-EPMC10242864 | biostudies-literature
Project description:The mechanisms for regulation of the Inhibitor of Apoptosis (IAP) Survivin in cells undergoing stress associated with tumor development and the tumor microenvironment are not well understood. The stress response transcription factors HIF-1α and Yin Yang 1 (YY1) were hypothesized to contribute to the upregulation of Survivin in tumor cells. As expected, U2OS cells overexpressing HIF-1α showed a 2- to 3-fold transactivation when transfected. Surprisingly, when YY1 was overexpressed in this survivin promoter reporter system, luciferase expression was repressed 30- to 40-fold. YY1 involvement in survivin promoter repression was confirmed using siRNA directed against YY1. These studies showed that knockdown of YY1 releases the survivin promoter from the observed repression and leads to a 3- to 5-fold increase in promoter activity above basal levels. A U2OS cell line containing a stable YY1 Tet-off system was used to determine whether a temporal increase in YY1 expression affects Survivin protein levels. A low to moderate decrease in Survivin protein was observed 24h and 48h after Tet removal. Studies also confirmed that YY1 is capable of directly binding to the survivin promoter. Collectively, these findings identify novel basal transcriptional requirements of survivin gene expression which are likely to play important roles in the development of cancer and resistance to its treatment.
| S-EPMC4071961 | biostudies-literature
Project description:The multifunctional protein Yin Yang 1 (YY1) has an important role in epigenetic regulation of gene expression. YY1 is highly expressed in various types of cancers, including prostate cancer. Currently, the mechanism underlying the functional role of YY1 in prostate tumorigenesis remains unclear. In this report, we investigated the functional interplay between YY1 and androgen receptor (AR), and the effect of YY1 on AR-mediated transcription. We found that YY1 physically interacts with AR both in a cell-free system and in cultured cells. YY1 is required for the optimal transcriptional activity of AR in promoting the transcription of the prostate-specific antigen (PSA) promoter. However, ectopic YY1 expression in LNCaP cells did not further enhance the reporter driven by the PSA promoter, suggesting that an optimal level of YY1 is already established in prostate tumor cells. Consistently, YY1 depletion in LNCaP cells reduced endogenous PSA levels, but overexpressed YY1 did not significantly increase PSA expression. We also observed that YY1-AR interaction is essential to YY1-mediated transcription activity of AR and YY1 is a necessary component in the complex binding to the androgen response element. Thus, our study demonstrates that YY1 interacts with AR and regulates its transcriptional activity.
| S-EPMC3668785 | biostudies-literature
Project description:Yin Yang 1 (YY1) is highly expressed in various types of cancers and regulates tumorigenesis through multiple pathways. In the present study, we evaluated YY1 expression levels in breast cancer cell lines, a breast cancer TMA, and two gene arrays. We observed that, compared with normal samples, YY1 is generally overexpressed in breast cancer cells and tissues. In functional studies, depletion of YY1 inhibited the clonogenicity, migration, invasion, and tumor formation of breast cancer cells, but did not affect the clonogenicity of nontumorigenic cells. Conversely, ectopically expressed YY1 enhanced the migration and invasion of nontumorigenic MCF-10A breast cells. In both a monolayer culture condition and a three-dimensional Matrigel system, silenced YY1 expression changed the architecture of breast cancer MCF-7 cells to that resembling MCF-10A cells, whereas ectopically expressed YY1 in MCF-10A cells had the opposite effect. Furthermore, we detected an inverse correlation between YY1 and p27 expression in both breast cancer cells and xenograft tumors with manipulated YY1 expression. Counteracting the changes in p27 expression attenuated the effects of YY1 alterations on these cells. In addition, YY1 promoted p27 ubiquitination and physically interacted with p27. In conclusion, our data suggest that YY1 is an oncogene and identify p27 as a new target of YY1.
| S-EPMC3828504 | biostudies-literature
Project description:Expression of the Snail gene is required for the epithelial-mesenchymal transitions that accompany mammalian gastrulation, neural crest migration, and organ formation. Pathologic expression of Snail contributes to the migratory capacity of invasive tumors, including melanomas. To investigate the mechanism of Snail up-regulation in human melanoma cells, a conserved enhancer located 3' of the Snail gene was analyzed. An overlapping Ets and yin yang 1 (YY1) consensus sequence, in addition to a SOX consensus sequence, was required for full enhancer activity. Proteins specifically binding these sequences were detected by electrophoretic mobility shift assay. The Ets/YY1 binding activity was purified by DNA-affinity chromatography and identified as YY1. Although ubiquitously expressed, YY1 was bound at the Snail 3' enhancer in vivo in Snail-expressing cells but not in cells that did not express Snail. Knockdown of YY1 in A375 cells led to decreased Snail expression. These results identify a role for YY1 in regulating transcription of Snail in melanoma cells through binding to the Snail 3' enhancer.
| S-EPMC2819842 | biostudies-literature
Project description:Survival of ovarian cancer patients is largely dictated by their response to chemotherapy, which depends on underlying molecular features of the malignancy. We previously identified YIN YANG 1 (YY1) as a gene whose expression is positively correlated with ovarian cancer survival. Herein, we investigated the mechanistic basis of this association. Epigenetic and genetic characteristics of YY1 in serous epithelial ovarian cancer were analyzed along with YY1 mRNA and protein. Patterns of gene expression in primary serous epithelial ovarian cancer and in the NCI60 database were investigated using computational methods. YY1 function and modulation of chemotherapeutic response in vitro was studied using small interfering RNA knockdown. Microarray analysis showed strong positive correlation between expression of YY1 and genes with YY1 and transcription factor E2F binding motifs in ovarian cancer and in the NCI60 cancer cell lines. Clustering of microarray data for these genes revealed that high YY1/E2F3 activity positively correlates with survival of patients treated with the microtubule-stabilizing drug paclitaxel. Increased sensitivity to taxanes, but not to DNA cross-linking platinum agents, was also characteristic of NCI60 cancer cell lines with a high YY1/E2F signature. YY1 knockdown in ovarian cancer cell lines results in inhibition of anchorage-independent growth, motility, and proliferation but also increases resistance to taxanes, with no effect on cisplatin sensitivity. These results, together with the prior demonstration of augmentation of microtubule-related genes by E2F3, suggest that enhanced taxane sensitivity in tumors with high YY1/E2F activity may be mediated by modulation of putative target genes with microtubule function.
| S-EPMC2675878 | biostudies-literature
Project description:Bone morphogenetic proteins (BMPs) were first studied as growth factors or morphogens of the transforming growth factor-beta superfamily. These growth molecules, originally associated with bone and cartilage development, are now known to play an important role in morphogenesis and homeostasis in many other tissues. More recently, significant contributions from BMPs, their receptors, and interacting molecules have been linked to carcinogenesis and tumor progression. On the other hand, BMPs can sometimes function as a tumor suppressor. Our report highlights these new roles in the pathogenesis of cancer that may suggest novel targets for therapeutic intervention.
| S-EPMC2939311 | biostudies-literature