Construction and comprehensive analysis of dysregulated long non‐coding RNA‐associated competing endogenous RNA network in clear cell renal cell carcinoma

Abstract

Objective This study aimed to assess the long noncoding RNA (lncRNA)‐microRNA (miRNA)‐messenger RNA (mRNA) regulatory network in clear cell renal cell carcinoma (ccRCC) by gene expression analyses. Materials and Methods LncRNA, miRNA, and mRNA expression profiles in ccRCC were obtained from The Cancer Genome Atlas. Differentially expressed lncRNAs, mRNAs (cut‐off: |log 2 [fold change, FC])| > 2.0 and adjusted P < 0.01) and miRNAs (|log 2FC| > 1.5 and adjusted P < 0.01) were unveiled using R. Cox regression analysis was performed to identify prognostic factors of ccRCC related to overall survival (OS). A protein‐protein interaction (PPI) network was constructed for differentially expressed mRNAs (DEmRNAs) by Search Tool for the Retrieval of Interacting Genes (STRING). Key hub genes were screened from top 300 DEmRNAs. LncRNA‐miRNA and miRNA‐mRNA regulatory network were constructed and combined into the competing endogenous RNA regulatory network. Gene ontology biological terms were screened by STRING; Kyoto Encyclopedia of Genes and Genomes pathways were identified using the “clusterProfiler” package in R. Results A total of 2331, 1517, and 83 DEmRNAs, lncRNAs, and miRNAs were identified, respectively. Eleven lncRNAs (AC016773.1, HOTTIP, LINC00460, NALCN‐AS1, PVT1, TRIM36‐IT1, WT1‐AS, COL18A1‐AS1, LINC00443, LINC00472, and TCL6), three miRNAs (hsa‐mir‐21, hsa‐mir‐144, and hsa‐mir‐155), and three mRNAs (COL4A4, NOD2, and GOLGA8B) were associated with OS. Specifically, four lncRNAs (PVT1, LINC00472, TCL6, and WT1‐AS1) and one mRNA (Collagen Type IV Alpha 4 Chain) were verified as independent prognostic factors by Gene Expression Profiling Interactive Analysis. Eleven key hub genes were obtained by PPI analysis. “Cell adhesion molecules (CAMs),” “chemical carcinogenesis,” and “cytokine‐cytokine receptor interaction” were significantly enriched in the network. Conclusion The findings clarify the pathogenesis of ccRCC and might provide potential therapeutic targets.

Identification of a three-long noncoding RNA prognostic model involved competitive endogenous RNA in kidney renal clear cell carcinoma

“…However, a rare study has explored the role of LINC00460 in KIRC, so this was the first study which found that high expression of LINC00460 is linked to poor prognosis in patients with KIRC. In the previous study, LINC00443 was reported as a tumor suppressor, which was associated with a better prognosis of KIRC, while MIAT was associated with worse prognosis [39][40][41]. In our study, expression and survival analysis of LINC00443 and MIAT revealed the high expression of MIAT and the low expression of LINC00443 in KIRC samples, which was related to poor prognosis and better prognosis, respectively.…”

Long Non-coding Wilms Tumor 1 Antisense RNA in the Development and Progression of Malignant Tumors

“…They found lower WT1-AS expression in ccRCC than in normal tissue, and WT1-AS expression level was significantly correlated with prognosis (23). Moreover, a subsequent study revealed that WT1-AS expression can be used as an independent predictor of ccRCC prognosis and that patients with high WT1-AS expression had poorer prognosis (24).…”

<p>Matrine Restrains Cell Growth and Metastasis by Up-Regulating LINC00472 in Bladder Carcinoma</p>

“…32 Furthermore, Liao Li et al pointed out MAT restrained BC cells by up-regulating vascular endothelial growth factor (VEGF) and Wang et al pointed out LINC00472 could be a diagnostic marker in renal tumor. 33 So we conjectured LINC0047 might be a potential treatment option in BC.…”