XAF1 expression levels in a non-small cell lung cancer cohort and its potential association with carcinogenesis

Schluckebier, Luciene; Aran, Veronica; Moraes, Joyce De; Paiva, H. B. R; Sternberg, Cinthya; Ferreira, Carlos Gil

doi:10.3892/or.2017.5680

Cited by 8 publications

(9 citation statements)

References 39 publications

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“…XAF1 has been well proven to be a tumor suppressor, which can promote the apoptosis of cancer cells 47 . Its expression was markedly reduced in NSCLC tumor samples 32 . Previous study confirmed that XAF1 overexpression can promote the apoptosis of A549 cells both in vivo and in vitro 48 .…”

Section: Discussionmentioning

confidence: 73%

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Gene Amplification-Driven Long Noncoding RNA SNHG17 Regulates Cell Proliferation and Migration in Human Non-Small-Cell Lung Cancer

Yan

Jiang

et al. 2019

Molecular Therapy - Nucleic Acids

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Lung cancer is the most common cancer all around the world, with high morbidity and mortality. Long noncoding RNA (lncRNA) has been reported to have a critical role in non-small-cell lung cancer (NSCLC) proliferation and migration. In the present study, we analyzed The Cancer Genome Atlas (TCGA) data, and we found that lncRNA Small Nucleolar RNA Host Gene 17 (SNHG17) was upregulated in NSCLC driven by the amplification of copy number, indicating the special role of SNHG17 in NSCLC. The full exact length of SNHG17 was determined by rapid amplification of cDNA ends (RACE). We modulated SNHG17 expression by RNAi and a series of functional assays were performed. Flow cytometry was used to explore the involvement of SNHG17 in NSCLC cell apoptosis. Results showed that the knockdown of SNHG17 inhibited the proliferation and migration and promoted the apoptosis of NSCLC cells. We acquired the global gene expression profile regulated by SNHG17 in A549 through RNA sequencing (RNA-seq) assays. We found 637 genes were upregulated while 581 genes were downregulated. We selected three genes (FOXA1, XAF1, and BIK) that were closely related to proliferation and apoptosis, and we confirmed their altered expression in A549 and PC-9 cells treated with small interfering RNA si-SNHG17. Our findings indicated gene amplification-driven lncRNA SNHG17 promotes cell proliferation and migration in NSCLC, suggesting its potential value as a biomarker in NSCLC.

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Section: Discussionmentioning

confidence: 73%

“…We selected three genes (FOXA1, 28 XAF1, 29 and BIK 30 ) that were closely related to proliferation and apoptosis. Reports demonstrated that FOXA1 31 was increased while XAF1 32 and BIK 33 were decreased in lung cancer. FOXA1 could be upregulated by lncRNA LOC730100 to promote cancer proliferation 34 .…”

Section: Resultsmentioning

confidence: 99%

Gene Amplification-Driven Long Noncoding RNA SNHG17 Regulates Cell Proliferation and Migration in Human Non-Small-Cell Lung Cancer

Yan

Jiang

et al. 2019

Molecular Therapy - Nucleic Acids

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“…It was demonstrated that XAF1 may promote cell apoptosis through in a multi-mechanism environment (44)(45)(46)(47). Down-regulated or deleted of XAF1 was observed in many malignancies, which suggesting that low expression of XAF1 may promote malignant tumor progression by relieving tumor cell apoptosis inhibition (48)(49)(50). However, XAF1 was up-regulated in testicular germ cell tumors exceptionally, which may lead to high sensitivity to chemotherapy (51).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of DNA methylation and gene expression reveals specific predictive biomarkers for renal cell carcinoma

Zhang¹,

Xu²,

Yin³

et al. 2020

Preprint

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Background We aimed to identify methylation-driven genes (MDGs) and predict the prognosis of clear cell renal cell carcinoma (ccRCC) based on several cohorts with high-throughput data.Methods The transcriptome profiles, 450K methylated data and corresponding clinical information were extracted from the cancer genome atlas (TCGA) database. MethylMix package was used to screen aberrant methylation events. Next, the Cox regression models were applied via survival package. Functional analysis was mainly performed based on ConsensusPathDB database. Besides, “mimifi” R package were adopted to analyze methylated alterations from three Gene Expression Omnibus (GEO) datasets. The predictive efficiency of constructed MDGs signature was assessed and validated in TCGA-KIRC and ICGC-RCC cohort, respectively. Unsupervised clustering analysis was conducted via ConsensusClusterPlus package. Moreover, MDGs-nomogram for OS prediction was conducted via glm and survival packages. Results Totally, we collected We finally identified 761 samples from TCGA-KIRC, ICGC-RCC, GSE61441, GSE105260 and GSE105261. We combined the expression data and 450K methylated data to find 5 hub prognostic MDGs (TAGLN2, PDK2, HHLA2, HOXA2, XAF1). We used the TCGA-KIRC cohort as the training dataset to verify the superior predictive significance of the 5 MDGs signature (AUC = 0.713), and validated it in ICGC-RCC cohort with AUC = 0.769. Kaplan-Meier analysis suggested that patients with high MDGs levels suffered from worse suvival outcomes. Besides, we further conducted the unsupervised clustering analysis in the whole ccRCC patients and identified the sub-cluster with the worst prognosis, indicating the MDGs could be used as efficient molecular classifier for ccRCC. We also identified 32 prognostic risk loci associated with hub MDGs in KIRC. Superior predictive efficiency was found in the MDGs-nomogram [Area Under Curve (AUC) of 3-year: 0.842, AUC of 5-year: 0.862], compared with traditional independent feature such as TNM stage (AUC of 3-year: 0.759, AUC of 5-year: 0.717). The 5 MDGs signature were mainly associated with oxygen metabolism, glycometabolism, even the HIF-1 signaling pathway. Conclusions Collectively, this study indicated several hub-MDGs and explored the prognostic value in ccRCC, which would provide new insights on the exploration of epigenetic pathogenesis and therapeutic targets for ccRCC.

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“…It is well known that, XAF1 as a proapoptotic tumor suppressor is always inactivated in multiple human cancers. XAF1 was identi ed ubiquitously in all normal adult and fetal tissues but was present in very low levels in a variety of cancer cell lines [41][42][43][44][45]. Both IFN-α2 and IFN-β were found to induce XAF1 transcription.…”

Section: Discussionmentioning

confidence: 99%

XAF1 is identified as a novel hub gene and associated with the clinical characteristics of lupus nephritis

Zeng¹,

Xie²,

Sun³

et al. 2020

Preprint

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Background Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) that is the most common cause of morbidity and mortality. At present, the definitive therapies towards LN remains to be elucidated, so illuminating the molecular mechanism behind the disease has become an urgent task for researchers. This study set out to screen the hub genes of LN. Methods The microarray expression profile dataset GSE32591 from the Gene Expression Omnibus (GEO) database with 15 normal and 32 LN samples was assessed in this study. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the LN-related differentially expressed genes (DEGs). The Nephroseq database was performed to identify correlation analysis between unexplored hub genes and clinical features of LN. Additionally, the expression of the candidate genes was detected in the kidney tissue by immunohistochemistry. Results The 14 genes (13 upregulated and 1 downregulated) ultimately screened out as candidate hub genes of the pathogenesis of LN. Moreover, Correlation analysis between the unexplored hub genes and clinical features of LN suggested that XAF1 may involve in the progression of LN. Finally, our data demonstrated that the expression level of XAF1 was upregulated in LN compared with IgA nephropathy (IgAN) and related to the WHO Lupus Nephritis Class and the quantitative 24 h proteinuria of LN patients. Conclusions The current study proposed XAF1 as a novel hub gene in LN which may perform as a brand-new biomarker or therapeutic target of LN in the future.

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XAF1 expression levels in a non-small cell lung cancer cohort and its potential association with carcinogenesis

Cited by 8 publications

References 39 publications

Gene Amplification-Driven Long Noncoding RNA SNHG17 Regulates Cell Proliferation and Migration in Human Non-Small-Cell Lung Cancer

Gene Amplification-Driven Long Noncoding RNA SNHG17 Regulates Cell Proliferation and Migration in Human Non-Small-Cell Lung Cancer

Comprehensive analysis of DNA methylation and gene expression reveals specific predictive biomarkers for renal cell carcinoma

XAF1 is identified as a novel hub gene and associated with the clinical characteristics of lupus nephritis

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