Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Competing endogenous RNA (ceRNA) network is dysregulated in the initiation and progression of tumors. In the present study, we explored the regulatory mechanism of ceRNA in endometrial carcinoma (EC) and the potential key molecules with potential value in the diagnosis, treatment, and prognosis of EC. The long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression profiles (552 EC tissues and 35 nontumor tissues) and microRNAs (miRNAs) expression profiles (546 EC tissues and 33 nontumor tissues) were downloaded from The Cancer Genome Atlas database to identify differentially expressed RNAs (DERNAs) in EC. An integrated bioinformatics analysis was used to construct an EC-specific ceRNA network and select key molecules. As a result, 96 differentially expressed lncRNAs (DElncRNAs), 29 differentially expressed miRNAs (DEmiRNAs), and 77 differentially expressed mRNAs (DEmRNAs) were identified. An EC-specific ceRNA network was built based on nine DElncRNAs significantly associated with overall survival. CCNB1 was found as a key gene in EC through the weighted gene coexpression network analysis and protein-protein interaction network analysis. Our ceRNA network showed C2orf48 and LINC00483 might upregulate CCNB1 via competing with miR-183. In addition, we found a subnetwork which contained survival-associated DERNAs (AC110491.1, LINC00483-miR-192-GRHL1). The results of reverse transcription quantitative polymerase chain reaction supported the relative expressions of C2orf48, LINC00483 were upregulated and that of AC110491.1 was downregulated in EC. We further found C2orf48 was upregulated in serous EC, endometrioid EC, and mixed serous and endometrioid EC. LINC00483 was upregulated in mixed serous and endometrioid EC compared with that in the normal tissues according to UALCAN database. In addition, candidate small molecular drugs were screened out by ConnectivityMap based on the 77 DEmRNAs in the ceRNA network. Eventually, C2orf48, LINC00483, and AC110491.1 were identified as three key lncRNAs in EC.
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PMID:Competing endogenous RNA network of endometrial carcinoma: A comprehensive analysis. 3105 98

BACKGROUND Long non-coding RNAs (lncRNAs) affect post-transcriptional regulation by interfering with microRNAs (miRNAs), and by acting as competitive endogenous RNAs (ceRNAs). The roles and mechanisms of lncRNAs as ceRNAs in the progression and prognosis of uterine corpus endometrial carcinoma are not well understood. MATERIAL AND METHODS We analyzed high-throughput transcriptome data downloaded from The Cancer Genome Atlas database for 548 patients with uterine corpus endometrial carcinoma, and the we constructed a ceRNA network. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses of differentially expressed messenger RNAs (DE-mRNAs) were performed using R software. Kaplan-Meier survival curves were generated for all RNAs in the ceRNA network. RESULTS We identified 2612 messenger RNAs (mRNAs), 1111 lncRNAs, and 187 miRNAs that were differentially expressed in uterine corpus endometrial carcinoma. We then identified mutual regulatory relationships between lncRNA-miRNA pairs and miRNA-mRNA pairs. A ceRNA regulatory network for uterine corpus endometrial carcinoma was successfully constructed, and consisted of 87 lncRNAs, 74 mRNAs, and 20 miRNAs. Nine lncRNAs, 3 miRNAs, and 22 mRNAs were associated with prognosis of uterine corpus endometrial carcinoma. We also analyzed the linear relationships between the expression of the 9 DE-lncRNAs and 22 DE-mRNAs with prognostic value. CONCLUSIONS Our study showed that the lncRNAs C2orf48 and LINC00261 might be key regulators of uterine corpus endometrial carcinoma and might serve as prognostic indicators. Our study contributes to the understanding of the molecular mechanisms of uterine corpus endometrial carcinoma, and it identifies lncRNAs that might serve as prognostic markers and therapeutic targets.
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PMID:Construction of a Competitive Endogenous RNA Network in Uterine Corpus Endometrial Carcinoma. 3165 Sep 84