Analysis of cyclin E co‐expression genes reveals nuclear transcription factor Y subunit alpha is an oncogene in gastric cancer

Bie, Liangyu; Li, Dan; Mu, Yu; Wang, Sheng; Chen, Beibei; Lyu, Hui-Fang; Han, Lili; Nie, Caiyun; Yang, Changcheng; Wang, Lin; Ren, Chuanchuan; Zhang, Weijie; Guo, Ping; Shi, Feng; Fan, Qingxia; Wang, Liuxing; Chen, Xiaobing; Luo, Suxia

doi:10.1016/j.cdtm.2018.07.003

Cited by 13 publications

(13 citation statements)

References 42 publications

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“…We examined the correlation between the expression levels of the 42 differentially expressed lncRNAs and each differentially expressed mRNA using two-sided Pearson correlation coefficients and the z-test. The mRNAs positively or negatively correlated with the 42 lncRNAs were considered to be lncRNA-related mRNAs (|Pearson correlation coefficient| > 0.4 [16][17][18][19][20] and P-value <0.05). The lncRNA-mRNA co-expression network was then constructed using Cytoscape V.3.8.5 (https://cytoscape.org/).…”

Section: Construction Of Co-expression Networkmentioning

confidence: 99%

The lncRNAs RP1-261G23.7, RP11-69E11.4 and SATB2-AS1 are a novel clinical signature for predicting recurrent osteosarcoma

et al. 2020

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Background: Osteosarcoma is the most common primary bone malignancy in children and adolescents. In order to find factors related to its recurrence, and thus improve recovery prospects, a powerful clinical signature is needed. Long noncoding RNAs (lncRNAs) are essential in osteosarcoma processes and development, and here we report significant lncRNAs to aid in earlier diagnosis of osteosarcoma. Methods: A univariate Cox proportional hazards regression analysis and a multivariate Cox regression analysis were used to analyze osteosarcoma patients’ lncRNA expression data from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET), a public database. Results: A lncRNA signature consisting of three lncRNAs (RP1-261G23.7, RP11-69E11.4 and SATB2-AS1) was selected. The signature was used to sort patients into high-risk and low-risk groups with meaningful recurrence rates (median recurrence time 16.80 vs. >128.22 months, log-rank test, P<0.001) in the training group, and predictive ability was validated in a test dataset (median 16.32 vs. >143.80 months, log-rank test, P=0.006). A multivariate Cox regression analysis showed that the significant lncRNA was an independent prognostic factor for osteosarcoma patients. Functional analysis suggests that these lncRNAs were related to the PI3K-Akt signaling pathway, the Wnt signaling pathway, and the G-protein coupled receptor signaling pathway, all of which have various, important roles in osteosarcoma development. The significant 3-lncRNA set could be a novel prediction biomarker that could aid in treatment and also predict the likelihood of recurrence of osteosarcoma in patients.

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Section: Construction Of Co-expression Networkmentioning

confidence: 99%

The lncRNAs RP1-261G23.7, RP11-69E11.4 and SATB2-AS1 are a novel clinical signature for predicting recurrent osteosarcoma

et al. 2020

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“…NF-Y has long been considered a ubiquitous transcription factor present at similar levels in normal and transformed cells; this view has largely changed, in part because of recent studies on the mRNA expression of its subunits in cancer. Data in ovarian [ 19 , 20 ], breast [ 21 ] and gastric [ 22 , 23 ] cancers indicated overexpression of NF-YA in tumors. Examination of the levels of NF-YA in cancer specimens present in The Cancer Genome Atlas (TCGA) by Firebrowse ( , accessed on 20 January 2020) suggested overexpression in epithelial tumors [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

NF-Y Subunits Overexpression in HNSCC

Bezzecchi

Bernardini

Ronzio

et al. 2021

Cancers

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NF-Y is the CCAAT-binding trimer formed by the histone fold domain (HFD), NF-YB/NF-YC and NF-YA. The CCAAT box is generally prevalent in promoters of “cancer” genes. We reported the overexpression of NF-YA in BRCA, LUAD and LUSC, and of all subunits in HCC. Altered splicing of NF-YA was found in breast and lung cancer. We analyzed RNA-seq datasets of TCGA and cell lines of head and neck squamous cell carcinomas (HNSCC). We partitioned all TCGA data into four subtypes, deconvoluted single-cell RNA-seq of tumors and derived survival curves. The CCAAT box was enriched in the promoters of overexpressed genes. The “short” NF-YAs was overexpressed in all subtypes and the “long” NF-YAl in Mesenchymal. The HFD subunits are overexpressed, except Basal (NF-YB) and Atypical (NF-YC); NF-YAl is increased in p53 mutated tumors. In HPV-positive tumors, high levels of NF-YAs, p16 and ΔNp63 correlate with better prognosis. Deconvolution of single cell RNA-seq (scRNA-seq) found a correlation of NF-YAl with Cancer Associated Fibroblasts (CAFs) and p-EMT cells, a population endowed with metastatic potential. We conclude that overexpression of HFD subunits and NF-YAs is protective in HPV-positive tumors; expression of NF-YAl is largely confined to mutp53 tumors and malignant p-EMT cells.

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“…The inactivation of NF-YA by RNAi leads to cell-cycle arrest and apoptosis in different cellular contexts, and no cell line has ever been described lacking NF-Y activity. On the other hand, our knowledge about the actual expression levels of NF-Y subunits in human tumors is still at a rudimentary stage: elevated expression of NF-YA was reported in cohorts of epithelial ovarian cancer [16,17], triple negative breast cancers [18], gastric cancer [19,20], and of the NF-YC subunit in gliomas and colon adenocarcinomas [21,22]. We recently started to interrogate, both in quantitative and qualitative way, the large RNA-seq datasets of TCGA and, surprisingly, found that NF-YA is overexpressed in most tumors of epithelial origin.…”

Section: Introductionmentioning

confidence: 99%

NF-YA Overexpression in Lung Cancer: LUSC

Bezzecchi

Ronzio

Dolfini

et al. 2019

Genes

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The CCAAT box is recognized by the trimeric transcription factor NF-Y, whose NF-YA subunit is present in two major splicing isoforms, NF-YAl (“long”) and NF-YAs (“short”). Little is known about the expression levels of NF-Y subunits in tumors, and nothing in lung cancer. By interrogating RNA-seq TCGA and GEO datasets, we found that, unlike NF-YB/NF-YC, NF-YAs is overexpressed in lung squamous cell carcinomas (LUSC). The ratio of the two isoforms changes from normal to cancer cells, with NF-YAs becoming predominant in the latter. NF-YA increased expression correlates with common proliferation markers. We partitioned all 501 TCGA LUSC tumors in the four molecular cohorts and verified that NF-YAs is similarly overexpressed. We analyzed global and subtype-specific RNA-seq data and found that CCAAT is the most abundant DNA matrix in promoters of genes overexpressed in all subtypes. Enriched Gene Ontology terms are cell-cycle and signaling. Survival curves indicate a worse clinical outcome for patients with increasing global amounts of NF-YA; same with hazard ratios with very high and, surprisingly, very low NF-YAs/NF-YAl ratios. We then analyzed gene expression in this latter cohort and identified a different, pro-migration signature devoid of CCAAT. We conclude that overexpression of the NF-Y regulatory subunit in LUSC has the scope of increasing CCAAT-dependent, proliferative (NF-YAshigh) or CCAAT-less, pro-migration (NF-YAlhigh) genes. The data further reinstate the importance of analysis of single isoforms of TFs involved in tumor development.

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Analysis of cyclin E co‐expression genes reveals nuclear transcription factor Y subunit alpha is an oncogene in gastric cancer

Cited by 13 publications

References 42 publications

The lncRNAs RP1-261G23.7, RP11-69E11.4 and SATB2-AS1 are a novel clinical signature for predicting recurrent osteosarcoma

The lncRNAs RP1-261G23.7, RP11-69E11.4 and SATB2-AS1 are a novel clinical signature for predicting recurrent osteosarcoma

NF-Y Subunits Overexpression in HNSCC

NF-YA Overexpression in Lung Cancer: LUSC

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