Visualizing and interpreting cancer genomics data via the Xena platform

Goldman, Mary; Craft, Brian; Hastie, Mim; Repečka, Kristupas; McDade, Fran; Kamath, Akhil; Banerjee, Ayan; Luo, Yunhai; Rogers, Dave; Brooks, Angela N.; Zhu, Jingchun; Haussler, David

doi:10.1038/s41587-020-0546-8

Cited by 2,206 publications

(1,537 citation statements)

References 18 publications

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“…Gene expression data in LUAD obtained from The Cancer Genome Atlas (TCGA) were retrieved on 6 March 2020 from the cBioPortal database ( ) [ 25 ], UCSC Xena platform ( ) [ 26 ] and Firebrowse ( ). The mRNA expression Z-scores and information on the clinical samples corresponding to LUAD patients were collected from cBioPortal.…”

Section: Methodsmentioning

confidence: 99%

FAM64A: A Novel Oncogenic Target of Lung Adenocarcinoma Regulated by Both Strands of miR-99a (miR-99a-5p and miR-99a-3p)

Mizuno

Tanigawa

Nohata

et al. 2020

Cells

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Lung adenocarcinoma (LUAD) is the most aggressive cancer and the prognosis of these patients is unfavorable. We revealed that the expression levels of both strands of miR-99a (miR-99a-5p and miR-99a-3p) were significantly suppressed in several cancer tissues. Analyses of large The Cancer Genome Atlas (TCGA) datasets showed that reduced miR-99a-5p or miR-99a-3p expression is associated with worse prognoses in LUAD patients (disease-free survival (DFS): p = 0.1264 and 0.0316; overall survival (OS): p = 0.0176 and 0.0756, respectively). Ectopic expression of these miRNAs attenuated LUAD cell proliferation, suggesting their tumor-suppressive roles. Our in silico analysis revealed 23 putative target genes of pre-miR-99a in LUAD cells. Among these targets, high expressions of 19 genes were associated with worse prognoses in LUAD patients (OS: p < 0.05). Notably, FAM64A was regulated by both miR-99a-5p and miR-99a-3p in LUAD cells, and its aberrant expression was significantly associated with poor prognosis in LUAD patients (OS: p = 0.0175; DFS: p = 0.0276). FAM64A knockdown using siRNAs suggested that elevated FAM64A expression contributes to cancer progression. Aberrant FAM64A expression was detected in LUAD tissues by immunostaining. Taken together, our miRNA-based analysis might be effective for identifying prognostic and therapeutic molecules in LUAD.

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Section: Methodsmentioning

confidence: 99%

FAM64A: A Novel Oncogenic Target of Lung Adenocarcinoma Regulated by Both Strands of miR-99a (miR-99a-5p and miR-99a-3p)

Mizuno

Tanigawa

Nohata

et al. 2020

Cells

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“…Moreover, we undertook bioinformatic analyses of the relationship between PD‐L1 mRNA expression and UCHL1 mRNA expression in NSCLC using microarray data from R2: Genomics Analysis and Visualization Platform (https://hgserver1.amc.nl/cgi-bin/r2/main.cgi) and RNA sequencing data from the UCSC Xena platform (http://xena.ucsc.edu/). 21 We found that there was a correlation between them (Figure ). To further elucidate the causes for the changed mRNA level of PD‐L1, we undertook a dual‐luciferase reporter assay to measure whether UCHL1 promoted the transcription of the PD‐L1 gene in NSCLC cells.…”

Section: Resultsmentioning

confidence: 70%

Ubiquitin C‐terminal hydrolase L1 promotes expression of programmed cell death‐ligand 1 in non‐small‐cell lung cancer cells

et al. 2020

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Programmed cell death‐ligand 1 (PD‐L1) expressed on cancer cells can cause immune escape of non‐small‐cell lung cancer (NSCLC). Elucidation of the regulatory mechanisms of the PD‐L1 expression is a prerequisite for establishing new tumor immunotherapy strategies. Ubiquitin C‐terminal hydrolase L1 (UCHL1) is a regulator of cellular signaling transduction that is aberrantly expressed in NSCLC. However, it is not known whether UCHL1 regulates the expression of PD‐L1 in NSCLC cells. In the present study, we found that UCHL1 promotes the expression of PD‐L1 in NSCLC cell lines. In addition, UCHL1 expressed in NSCLC cells inhibited activation of Jurkat cells through upregulation of PD‐L1 expression in in vitro experiments. Moreover, UCHL1 upregulates PD‐L1 expression through facilitating activation of the AKT‐P65 signaling pathway. In conclusion, these results indicated that UCHL1 promoted PD‐L1 expression in NSCLC cells. This finding implied that inhibition of UCHL1 might suppress immune escape of NSCLC through downregulation of PD‐L1 expression in NSCLC cells.

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“…Expression and methylation data of TCGA samples were downloaded from XENA data repository [ 40 ]. To evaluate the magnitude and significance of the association between LRP5 mRNA expression and promoter methylation in TCGA samples we calculated the Spearman’s rank correlation rho and performed a correlation test.…”

Section: Methodsmentioning

confidence: 99%

TRAP1 Regulates Wnt/β-Catenin Pathway through LRP5/6 Receptors Expression Modulation

Lettini

Condelli

Pietrafesa

et al. 2020

IJMS

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Wnt/β-Catenin signaling is involved in embryonic development, regeneration, and cellular differentiation and is responsible for cancer stemness maintenance. The HSP90 molecular chaperone TRAP1 is upregulated in 60–70% of human colorectal carcinomas (CRCs) and favors stem cells maintenance, modulating the Wnt/β-Catenin pathway and preventing β-Catenin phosphorylation/degradation. The role of TRAP1 in the regulation of Wnt/β-Catenin signaling was further investigated in human CRC cell lines, patient-derived spheroids, and CRC specimens. TRAP1 relevance in the activation of Wnt/β-Catenin signaling was highlighted by a TCF/LEF Cignal Reporter Assay in Wnt-off HEK293T and CRC HCT116 cell lines. Of note, this regulation occurs through the modulation of Wnt ligand receptors LRP5 and LRP6 that are both downregulated in TRAP1-silenced cell lines. However, while LRP5 mRNA is significantly downregulated upon TRAP1 silencing, LRP6 mRNA is unchanged, suggesting independent mechanisms of regulation by TRAP1. Indeed, LRP5 is regulated upon promoter methylation in CRC cell lines and human CRCs, whereas LRP6 is controlled at post-translational level by protein ubiquitination/degradation. Consistently, human CRCs with high TRAP1 expression are characterized by the co-upregulation of active β-Catenin, LRP5 and LRP6. Altogether, these data suggest that Wnt/β-Catenin signaling is modulated at multiple levels by TRAP1.

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Visualizing and interpreting cancer genomics data via the Xena platform

Cited by 2,206 publications

References 18 publications

FAM64A: A Novel Oncogenic Target of Lung Adenocarcinoma Regulated by Both Strands of miR-99a (miR-99a-5p and miR-99a-3p)

FAM64A: A Novel Oncogenic Target of Lung Adenocarcinoma Regulated by Both Strands of miR-99a (miR-99a-5p and miR-99a-3p)

Ubiquitin C‐terminal hydrolase L1 promotes expression of programmed cell death‐ligand 1 in non‐small‐cell lung cancer cells

TRAP1 Regulates Wnt/β-Catenin Pathway through LRP5/6 Receptors Expression Modulation

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