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.

Pseudogene-Derived lncRNAs and Their miRNA Sponging Mechanism in Human Cancer

“…They also showed that DUXAP10 was positively correlated with poor prognosis and epigenetically silenced p21 by recruiting EZH2 to the promoter of p21, thereby promoting cell proliferation and metastasis. Chen et al (2019) demonstrated that DUXAP8 and DUXAP9 were significantly upregulated in renal cell carcinoma, promoted tumor growth and served as two unfavorable prognostic biomarkers for patients with renal cell carcinoma. DUXAP8 was also discovered to enhance progression of renal cell carcinoma (Huang T. et al, 2018).…”

“…To date, two DUXA-associated pseudogene-derived lncRNAs, DUXAP8 and DUXAP9, have been discovered to act as ceRNAs to enhance cancer development. For example, Chen et al (2019) demonstrated that DUXAP8 and DUXAP9 enhanced growth of renal cell carcinoma by binding to miR-29c-3p and leading to upregulation of COL1A1 and COL1A2; Huang T. et al (2018) suggested that DUXAP8 facilitated progression of renal cell carcinoma by sponging miR-126. DUXAP8, upregulated by STAT3, also fueled migration and invasion of colorectal cancer by functioning as a ceRNA for miR-577 to regulate RAB14 (Du et al, 2019).…”

A miRNA-clinicopathological nomogram for the prediction of central lymph node metastasis in papillary thyroid carcinoma-analysis from TCGA database

“…SLC6A1 and COL1A2 are unfavorable prognostic markers in renal cancer. [ 40 , 41 ] SYT1 promotes colon cancer cell proliferation, migration, and invasion. [ 42 ] COL19A1 encodes the alpha chain of type XIX collagen, but the function of this collagen is not well known.…”

Identification of long non-coding RNA signatures for squamous cell carcinomas and adenocarcinomas

“…In the meantime, high expression of this gene is related to a poor prognosis. In addition to this study, this lncRNA has been linked to several other cancer types, renal cell carcinoma [ 40 ] and colon cancer [ 33 ], for example. For SCCs specifically, it is linked to esophageal squamous cell carcinoma [ 37 ].…”