Competing endogenous RNA network of endometrial carcinoma: A comprehensive analysis

Abstract

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.

Comprehensive bioinformatic analyses of lncRNA-mediated ceRNA network for uterine corpus endometrial carcinoma

“…As shown in our ceRNA subnetwork diagram for TCGA, lncRNAs such as LINC00443, C2orf48, LINC00483 could regulate DLX4 and NR3C1 expression by binding to miR-183. LINC00443, LINC00483 and C2orf48 were previously proved to promote carcinoma progression (35), the same consequence of which were validated by our experiment. DLX4 has been shown to cause tumor migration, invasion, and metastasis (36).…”

Identification of the Prognostic LncRNA Biomarkers and Comprehensive Analysis of LncRNA-Mediated ceRNA Network for Uterine Corpus Endometrial Carcinoma

“…As shown in our ceRNA subnetwork diagram for TCGA, lncRNAs such as LINC00443, C2orf48, LINC00483 could regulate DLX4 and NR3C1 expression by binding to miR-183. LINC00443, LINC00483 and C2orf48 were previously proved to promote carcinoma progression [35], the same consequence of which were validated by our experiment. DLX4 has been shown to cause tumor migration, invasion, and metastasis [36].…”

Towards Personalized Medicine: Non-Coding RNAs and Endometrial Cancer

“…In this context, TCGA work has represented an epochal turning point for cancer patients' personalized management, allowing it to be selected according to genetic and In the epigenetic risk factors box, the ncRNAs are listed in alphabetical order. The data in the figure are retrieved from references [2][3][4]26,30,35,36,38,63,65,77,82,84,[95][96][97].…”

“…In the epigenetic risk factors box, the ncRNAs are listed in alphabetical order. The data in the figure are retrieved from references [2][3][4]26,30,35,36,38,63,65,77,82,84,95,96,97].…”