Competing endogenous RNA network of endometrial carcinoma: A comprehensive analysis

• Published in: Journal of cellular biochemistry 2019-09, Vol.120 (9), p.15648-15660
• Main Authors: Liu, Jinhui, Nie, Sipei, Liang, Junya, Jiang, Yi, Wan, Yicong, Zhou, Shulin, Cheng, Wenjun
• Format: Article
• Language: English
• Subjects: Bioinformatics; bioinformatics analysis; Cancer; Carcinoma; competing endogenous RNA network; Drug development; Endometrial cancer; endometrial carcinoma; Endometrium; Genomes; long noncoding RNA; Medical prognosis; miRNA; Network analysis; Polymerase chain reaction; Proteins; Regulatory mechanisms (biology); Reverse transcription; reverse transcription quantitative polymerase chain reaction; Ribonucleic acid; RNA; Survival; Tissues; Tumors; Uterine cancer
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.28831

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. In this study, we built an endometrial carcinoma (EC)‐specific competing endogenous RNA (ceRNA) network and explored the regulation mechanism of ceRNA in EC by using an integrated bioinformatics analysis. And we found three novel key long noncoding RNAs (lncRNAs), which might serve as diagnostic or prognostic biomarkers and potential therapeutic targets in EC.