GSCALite: a web server for gene set cancer analysis

Liu, Chunjie; Hu, Fei; Xia, Meng; Han, Leng; Zhang, Qiong; Guo, An‐Yuan

doi:10.1093/bioinformatics/bty411

Cited by 701 publications

(557 citation statements)

References 13 publications

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“…Finally, since bioinformatics analyses and our experimental results show discrepancies in the relationship between SOD1 and miR-409-3p (especially the correlation between SOD1 and miR-409-3p was not significant in ADC), we used another method, GSCA Lite software (Liu et al, 2018) to analyze the association between SOD1 and miR-409-3p and determine whether other factors are involved in the regulation of SOD1 expression by miR-409-3p. As shown in Figure 5A, 90 transcription factors related to lung cancer were identified by this analysis, and 12 were highly co-expressed with SOD1, of which only SETDB1 could be regulated by miR-409-3p.…”

Section: Setdb1 May Contribute To the Relationship Between Mir-409-3pmentioning

confidence: 99%

SOD1 Promotes Cell Proliferation and Metastasis in Non-small Cell Lung Cancer via an miR-409-3p/SOD1/SETDB1 Epigenetic Regulatory Feedforward Loop

Liu

et al. 2020

Front. Cell Dev. Biol.

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Superoxide dismutase 1(SOD1) is a major antioxidant with oncogenic effects in many human cancers. Although SOD1 is overexpressed in various cancers, the clinical significance and functions of SOD1 in non-small cell lung cancer (NSCLC), particularly the epigenetic regulation of SOD1 in NSCLC carcinogenesis and progression have been less well investigated. In this study, we found that SOD1 expression was upregulated in NSCLC cell lines and tissues. Further, elevated SOD1 expression could promote NSCLC cell proliferation, invasion and migration. While inhibition of SOD1 expression induced NSCLC G1-phase cell cycle arrest and promoted apoptosis. In addition, miR-409-3p could repress SOD1 expression and significantly counteract its oncogenic activities. Bioinformatics analysis indicated that SET domain bifurcated histone lysine methyltransferase1 (SETDB1) was involved in the epigenetic regulation of miR-409-3p and SOD1 expression and functions in NSCLC cells. Identification of this miR-409-3p/SOD1/SETDB1 epigenetic regulatory feedforward loop may provide new insights into further understanding of NSCLC tumorigenesis and progression. Additionally, our results incicate that SOD1 may be a potential new therapeutic target for NSCLC treatment.

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Section: Setdb1 May Contribute To the Relationship Between Mir-409-3pmentioning

confidence: 99%

SOD1 Promotes Cell Proliferation and Metastasis in Non-small Cell Lung Cancer via an miR-409-3p/SOD1/SETDB1 Epigenetic Regulatory Feedforward Loop

Liu

et al. 2020

Front. Cell Dev. Biol.

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“…1a). At the cancer level, netrins associated with uterine corpus endometrial carcinoma (UCEC) exhibited the highest number of mutations (54), followed by colon adenocarcinoma (COAD) (49), skin cutaneous melanoma (SKCM) (47), stomach adenocarcinoma (STAD) (42), lung adenocarcinoma (LUAD) (38), and lung squamous cell carcinoma (LUSC) (36). The total mutation rates of Netrin family members in the above six cancers were 10.19%, 12.28%, 10.06%, 9.61%, 6.70% and 7.32%, respectively.…”

Section: Mutation and Fusion Gene Analysis Of Netrin Family In Pan-camentioning

confidence: 99%

“…We analyzed the methylation of the NTN family members and their downstream genes in TCGA 33 cancers using GSCALite 36 (Fig. 5a-c).…”

Section: Methylation and Clinical Analysis Of Netrins In Pan-cancermentioning

confidence: 99%

The pan-cancer landscape of netrin family reveals potential oncogenic biomarkers

Hao

Lin

et al. 2020

Sci Rep

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Recent cancer studies have found that the netrin family of proteins plays vital roles in the development of some cancers. However, the functions of the many variants of these proteins in cancer remain incompletely understood. In this work, we used the most comprehensive database available, including more than 10000 samples across more than 30 tumor types, to analyze the six members of the netrin family. We performed comprehensive analysis of genetic change and expression of the netrin genes and analyzed epigenetic and pathway relationships, as well as the correlation of expression of these proteins with drug sensitivity. Although the mutation rate of the netrin family is low in pan-cancer, among the tumor patients with netrin mutations, the highest number are Uterine Corpus Endometrial Carcinoma patients, accounting for 13.6% of cases (54 of 397). Interestingly, the highest mutation rate of a netrin family member is 38% for NTNG1 (152 of 397). Netrin proteins may participate in the development of endocrine-related tumors and sex hormone-targeting organ tumors. Additionally, the participation of NTNG1 and NTNG2 in various cancers shows their potential for use as new tumor markers and therapeutic targets. this analysis provides a broad molecular perspective of this protein family and suggests some new directions for the treatment of cancer. Cytokines, growth factors, angiogenic factors, and extracellular proteases are secreted to the outside of the cell to produce biological functions 1. These secreted proteins participate in the immune regulation of chronic inflammation 2,3 and the occurrence of lipid metabolism diseases 4 , but also play important roles in tumor invasion, metastasis, immunity, and drug resistance 5-8. For example, CD317 and EGFR are secreted proteins that are potential diagnostic markers for non-small cell lung cancer 9. CD63 is secreted by melanoma into the blood and can be used as a protein marker 10. HGF inhibits the treatment of RAF inhibitors of BRAF mutant melanoma 11. The netrins are neuroguiding factors with axonal guiding function, and are similar to laminin in structure. Netrins were first discovered in C. elegans in 1990 12 , and this family of proteins includes the secreted proteins Netrin-1 (NTN1), Netrin-3 (NTN3), Netrin-4 (NTN4), and Netrin-5 (NTN5). The secreted proteins have a common domain structure, with an N-terminal laminin repeat (Laminin N-terminal), three cysteine-rich EGF modules (V-1, V-2, and V-3), and a positively charged C-terminal domain (NTR) 13. The netrin family also includes two membrane-binding proteins, Netrin-G1 (NTNG1) and Netrin-G2 (NTNG2) 14. Although these proteins also have Laminin N-terminal and Laminin EGF domains, their ends have different functions due to GPI 15. The major binding receptors of the secreted netrin proteins are DCC and UNC5 homologue family UNC5A-D, which are both dependent receptors. Netrin binding to a receptor promotes cell survival, proliferation, and differentiation, and without netrin binding, the receptor induces apoptosis 16,17....

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“…S1). Basing on the Gene Set Cancer Analysis (GSCA) web server [8], we further assessed the gene set differential expression profiles among 14 cancer types with available paired tumor-normal tissue expression data. Across multiple cancer types, the differentially expressed genes (upregulated or downregulated) included both m 6 A and 5mC regulators ( Supplementary Fig.…”

mentioning

confidence: 99%

Identification of cross-talk between m6A and 5mC regulators associated with onco-immunogenic features and prognosis across 33 cancer types

et al. 2020

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Methylation of RNA and DNA, notably in the forms of N6-methyladenosine (m 6 A) and 5-methylcytosine (5mC) respectively, plays crucial roles in diverse biological processes. Currently, there is a lack of knowledge regarding the cross-talk between m 6 A and 5mC regulators. Thus, we systematically performed a pan-cancer genomic analysis by depicting the molecular correlations between m 6 A and 5mC regulators across~11,000 subjects representing 33 cancer types. For the first time, we identified cross-talk between m 6 A and 5mC methylation at the multiomic level. Then, we further established m 6 A/5mC epigenetic module eigengenes by combining hub m 6 A/5mC regulators and informed a comprehensive epigenetic state. The model reflected status of the tumor-immune-stromal microenvironment and was able to predict patient survival in the majority of cancer types. Our results lay a solid foundation for epigenetic regulation in human cancer and pave a new road for related therapeutic targets.

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GSCALite: a web server for gene set cancer analysis

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 701 publications

References 13 publications

SOD1 Promotes Cell Proliferation and Metastasis in Non-small Cell Lung Cancer via an miR-409-3p/SOD1/SETDB1 Epigenetic Regulatory Feedforward Loop

SOD1 Promotes Cell Proliferation and Metastasis in Non-small Cell Lung Cancer via an miR-409-3p/SOD1/SETDB1 Epigenetic Regulatory Feedforward Loop

The pan-cancer landscape of netrin family reveals potential oncogenic biomarkers

Identification of cross-talk between m6A and 5mC regulators associated with onco-immunogenic features and prognosis across 33 cancer types

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