Dataset Information

Overexpressed pseudogenes, DUXAP8 and DUXAP9, promote growth of renal cell carcinoma and serve as unfavorable prognostic biomarkers.

ABSTRACT: BACKGROUND:Growing studies have reported that pseudogenes play key roles in multiple human cancers. However, expression and roles of pseudogenes in renal cell carcinoma remains absent. RESULTS:31 upregulated and 16 downregulated pseudogenes were screened. Higher expression of DUXAP8 and DUXAP9 indicated poorer prognosis of kidney cancer. 33 and 5 miRNAs were predicted to potentially binding to DUXAP8 and DUXAP9, respectively. miR-29c-3p was identified as the most potential binding miRNAs of DUXAP8 and DUXAP9 based on expression, survival and correlation analyses. 254 target genes of miR-29c-3p were forecast. 47 hub genes with node degree >= 10 were identified. Subsequent analysis for the top 10 hub genes demonstrated that COL1A1 and COL1A2 may be two functional targets of DUXAP8 and DUXAP9. Expression of DUXAP8, DUXAP9, COL1A1 and COL1A2 were significantly increased in cancer samples compared to normal controls while miR-29c-3p expression was decreased. Luciferase reporter assay revealed that miR-29c-3p could directly bind to DUXAP8, DUXAP9, COL1A1 and COL1A2. Functional experiments showed that DUXAP8 and DUXAP9 enhanced but miR-29c-3p weakened growth of renal cell carcinoma. CONCLUSIONS:In conclusion, upregulated DUXAP8 and DUXAP9 promote growth of renal cell carcinoma and serve as two promising prognostic biomarkers. METHODS:Dysregulated pseudogenes were obtained by dreamBase and GEPIA. The binding miRNAs of pseudogene and targets of miRNA were predicted using starBase and miRNet. Kaplan-Meier plotter was utilized to perform survival analysis, and Enrichr database was introduced to conduct functional enrichment analysis. Hub genes were identified through STRING and Cytoscape. qRT-PCR, luciferase reporter assay, cell counting assay and colony formation assay were performed to validate in silico analytic results.

SUBMITTER: Chen J

PROVIDER: S-EPMC6710046 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Overexpressed pseudogenes, DUXAP8 and DUXAP9, promote growth of renal cell carcinoma and serve as unfavorable prognostic biomarkers.

Chen Jing J Lou Weiyang W Ding Bisha B Wang Xian X

Aging 20190813 15

<h4>Background</h4>Growing studies have reported that pseudogenes play key roles in multiple human cancers. However, expression and roles of pseudogenes in renal cell carcinoma remains absent.<h4>Results</h4>31 upregulated and 16 downregulated pseudogenes were screened. Higher expression of DUXAP8 and DUXAP9 indicated poorer prognosis of kidney cancer. 33 and 5 miRNAs were predicted to potentially binding to DUXAP8 and DUXAP9, respectively. miR-29c-3p was identified as the most potential binding ...[more]

PMID: 31409759

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Project description:ObjectiveThis study aims to identify potential prognostic and therapeutic biomarkers in papillary renal cell carcinoma (pRCC).MethodsTwo microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified. The protein-protein interaction (PPI) networks and functional annotations of DEGs were established. Survival analysis was utilized to evaluate the prognostic significance of the DEGs and the association between the expression level of candidate biomarkers and various tumour-infiltrating immune cells was explored. The role of PTTG1 in tumour microenvironments (TME) was further explored using Single-cell RNA-seq and its prognostic and therapeutic significance was validated in Fudan University Shanghai Cancer Centre (FUSCC) cohort.ResultsEight genes, including BUB1B, CCNB1, CCNB2, MAD2L1, TTK, CDC20, PTTG1, and MCM were found to be negatively associated with patients' prognosis. The expression level of PTTG1 was found to be significantly associated with lymphocytes, immunomodulators, and chemokine in the TCGA cohort. Single-cell RNA-seq information indicated that PTTG1 was strongly associated with the proliferation of T cells. In the FUSCC cohort, the expression level of PTTG1 was also statistically significant for both progression-free survival (PFS) and overall survival (OS) prediction (HR = 2.683, p < .001; HR = 2.673, p = .001). And higher expression level of PTTG1 was significantly associated with immune checkpoint blockade (ICB) response in the FUSCC cohort (χ2=3.99, p < .05).ConclusionsEight genes were identified as a prognostic biomarker and the expression level of PTTG1 was also found to serve as a potential predictor for ICB response in pRCC patients.Key messages:Eight genes, including BUB1B, CCNB1, CCNB2, MAD2L1, TTK, CDC20, PTTG1, and MCM were found to be negatively associated with pRCC patients' prognosis.Expression level of PTTG1 was significantly associated with tumour microenvironment including lymphocytes, immunomodulators, and chemokines.Higher expression level of PTTG1 was significantly associated with immune checkpoint blockade (ICB) response in FUSCC cohort.

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Dataset Information

Overexpressed pseudogenes, DUXAP8 and DUXAP9, promote growth of renal cell carcinoma and serve as unfavorable prognostic biomarkers.

Publications

Overexpressed pseudogenes, DUXAP8 and DUXAP9, promote growth of renal cell carcinoma and serve as unfavorable prognostic biomarkers.

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