A Simple Competing Endogenous RNA Network Identifies Novel mRNA, miRNA, and lncRNA Markers in Human Cholangiocarcinoma

Zhang, Cheng; Ge, Chunlin

doi:10.1155/2019/3526407

Cited by 12 publications

(8 citation statements)

References 41 publications

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“…The upregulation of MST1R promotes the progression of many epithelial cancers, including pancreatic, lung, and breast cancer [46–48]. We previously demonstrated that MST1R is upregulated and associated with overall survival in CCA [49]. However, the underlying mechanisms regulating MST1R remain largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

Zhang

Meng

et al. 2019

Cancer Cell Int

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Background: The incidence of cholangiocarcinoma (CCA) has risen in recent years, and it has become a significant health burden worldwide. However, the mechanisms underlying tumorigenesis and progression of this disease remain largely unknown. An increasing number of studies have demonstrated crucial biological functions of epigenetic modifications, especially DNA methylation, in CCA. The present study aimed to identify and analyze methylationregulated differentially expressed genes (MeDEGs) involved in CCA tumorigenesis and progression by bioinformatics analysis. Methods:The gene expression profiling dataset (GSE119336) and gene methylation profiling dataset (GSE38860) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified using the limma packages of R and GEO2R, respectively. The MeDEGs were obtained by overlapping the DEGs and DMGs. Functional enrichment analyses of these genes were then carried out. Protein-protein interaction (PPI) networks were constructed using STRING and visualized in Cytoscape to determine hub genes. Finally, the results were verified based on The Cancer Genome Atlas (TCGA) database. Results:We identified 98 hypermethylated, downregulated genes and 93 hypomethylated, upregulated genes after overlapping the DEGs and DMGs. These genes were mainly enriched in the biological processes of the cell cycle, nuclear division, xenobiotic metabolism, drug catabolism, and negative regulation of proteolysis. The top nine hub genes of the PPI network were F2, AHSG, RRM2, AURKB, CCNA2, TOP2A, BIRC5, PLK1, and ASPM. Moreover, the expression and methylation status of the hub genes were significantly altered in TCGA. Conclusions:Our study identified novel methylation-regulated differentially expressed genes (MeDEGs) and explored their related pathways and functions in CCA, which may provide novel insights into a further understanding of methylation-mediated regulatory mechanisms in CCA.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

Zhang

Meng

et al. 2019

Cancer Cell Int

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“…COL18A1 Antisense RNA 1 (COL18A1-AS1), is a lncRNA located in 21q22.3. Some bioinformatics analysis has reported that COL18A1-AS1 could be a biomarker for Cholangiocarcinoma [ 23 , 24 ] and RCC [ 25 , 26 ]. Gene Set Enrichment Analysis (GSEA) showed that COL18A1-AS1 might participated in lipid metabolism signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Restoring the epigenetically silenced lncRNA COL18A1-AS1 represses ccRCC progression by lipid browning via miR-1286/KLF12 axis

et al. 2022

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Abnormal accumulation of lipids has been highlighted in the progression of clear cell renal cell carcinoma (ccRCC). However, the underlying mechanism remains unclear. Emerging evidence suggests long noncoding RNAs (lncRNAs) participate in the regulation of lipid metabolism. In this study, we found lncRNA COL18A1-AS1 was downregulated in ccRCC and that higher COL18A1-AS1 expression indicated better prognosis. Decreased COL18A1-AS1 expression was caused by DNA methylation at the CpG islands within its promoter. Restoring the epigenetically silenced COL18A1-AS1 repressed tumor progression, promoted lipid browning and consumption in vitro and in vivo. Mechanistically, COL18A1-AS1 could competitively bind miR-1286 to increase the expression of Krüppel-like factor 12 (KLF12). Downregulation of COL18A1-AS1 in ccRCC resulted in the low expression of KLF12. COL18A1-AS1/KLF12 positively regulated uncoupling protein 1 (UCP1)–mediated lipid browning, which promotes tumor cell “slimming” and inhibits tumor progression. When tumor cell “slimming” occurred, lipid droplets turned into tiny pieces, and lipids were consumed without producing ATP energy. Taken together, our findings on COL18A1-AS1-miR-1286/KLF12 axis revealed a potential mechanism of abnormal accumulation of lipids in ccRCC and could be a promising therapeutic target for ccRCC patients.

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“…The molecular chemical signals released from these pseudo-synapses are a likely cause of breast cancer brain metastasis [42][43][44][45]. An analysis of the TCGA database has also implicated GRID2IP as a novel prognostic marker in patients with cholangiocarcinoma [46]. TMEM117 is a six transmembrane protein with a conserved sequence; it is present in pro-and anti-apoptotic BCL-2 family of proteins.…”

Section: Discussionmentioning

confidence: 99%

A four-DNA methylation signature as a novel prognostic biomarker for survival of patients with gastric cancer

Zheng

et al. 2020

Cancer Cell Int

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Background: Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancerrelated mortality. Lack of prognostic indicators for patient survival hinders GC treatment and survival. Methods and results:Methylation profile data of patients with GC obtained from The Cancer Genome Atlas (TCGA) database were analyzed to identify methylation sites as biomarkers for GC prognosis. The cohort was divided into training and validation sets. Univariate Cox, LASSO regression,and multivariate Cox analyses revealed a close correlation of a four-DNA methylation signature as a risk score model with the overall survival of patients with GC. The survival between high-risk and low-risk score patients with GC was significantly different. Analyses of receiver operating characteristics revealed a high prognostic accuracy of the four-DNA methylation signature in patients with GC. The subgroup analysis indicated that the accuracy included that for anatomical region, histologic grade, TNM stage, pathological stage, and sex. The GC prognosis based on the four-DNA methylation signature was more precise than that based on known biomarkers. Conclusions:The four-DNA methylation signature could serve as a novel independent prognostic factor that could be an important tool to predict the prognostic outcome of GC patients. This potential must be verified in a large-scale population cohort study and through basic research studies.

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A Simple Competing Endogenous RNA Network Identifies Novel mRNA, miRNA, and lncRNA Markers in Human Cholangiocarcinoma

Cited by 12 publications

References 41 publications

Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

Restoring the epigenetically silenced lncRNA COL18A1-AS1 represses ccRCC progression by lipid browning via miR-1286/KLF12 axis

A four-DNA methylation signature as a novel prognostic biomarker for survival of patients with gastric cancer

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