Identification of long noncoding RNA RP11-89K21.1 and RP11-357H14.17 as prognostic signature of endometrial carcinoma via integrated bioinformatics analysis

Gao, Lingling; Nie, Xin; Zhang, Wenchao; Gou, Rui; Hu, Yuexin; Qi, Yuanlin; Li, Xiao; Liu, Qing; Liu, Juanjuan; Lin, Bei

doi:10.21203/rs.3.rs-23177/v1

Cited by 4 publications

(4 citation statements)

References 46 publications

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“…The constructed lncRNA-miRNA-Top10 hub gene network diagram showed that lncRNA RP11-366F6 regulated hsa-miR-143, and hsa-miR-143 further regulated LEFTY1 and LIN28A; lncRNA CTD-2314B22 regulated hsa-miR-143 and hsa-miR-424, further regulated downstream LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 genes; lncRNA FRMD6-AS2 regulated hsa-miR-96, hsa-miR-182, and hsa-miR-211 and further regulated downstream FBXO32, DCN, ANGPTL1, ADRA1A, and KCNMA1 genes; RP11-89 K21 regulated hsa-miR-143 and hsa-miR-424 further regulated downstream LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55, among which CTD-2314B22 and RP11-89 K21 can simultaneously regulate hsa-miR-143 and hsa-miR-424 and downstream LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 genes. It has been illustrated that the expression of CTD-2314B22 in endometrial carcinoma is superior to that in normal tissues [36]; lncRNA FRMD6-AS2 can impede the growth of endometrial cancer cells by increasing FRMD6 in endometrial cancer cells [37]; hsa-miR-143 is able to impede the adhesion, migration, and epithelial-mesenchymal transformation of…”

Section: Discussionmentioning

confidence: 99%

Construction of Endometrial Carcinoma ceRNA Network and Screening of Key Genes Based on TCGA Database

Song

Chu

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. Long noncoding RNA (lncRNA) has received more and more attention in human tumor research. This study is aimed at clarifying the regulatory network of lncRNAs-microRNAs- (miRNAs-) mRNAs and at determining the relevant targets in the development of endometrial cancers. Methods. Download the miRNA, mRNA, and lncRNA expression profile data of endometrial cancer patients from TCGA; use the “DESeq2” package of R software to identify the differential expression of miRNAs, mRNAs, and lncRNAs; construct a network of ceRNA; and perform gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment assessment on mRNAs in the network of ceRNA; string and Cytoscape 3.7.2 perform PPI assessment on target genes and TOP 10 hub gene screening; Cytoscape 3.7.2 computer program was employed for constructing the lncRNA-miRNA-TOP10 hub mRNA network diagram to determine the signal axis; StarBase database to verify the Top10 hub mRNA expression; the “survival” package in R computer program was implemented to analyze the survival rate of all genes on the lncRNA-miRNA-Top10 hub mRNA network diagram; RT-qPCR to verify the expression level of genes on the signal axis. Results. 1119 differential mRNAs, 14 differential lncRNAs, and 65 differential miRNAs were screened in TCGA; we constructed a ceRNA regulatory network composed of 5 DELs, 7 DEMs, and 90 DEGs; String combined with Cytoscape to screen out Top10 hub genes, namely: LEFTY1, LIN28A, LHX3, ST8SIA3, CEP55, FBXO32, DCN, ANGPTL1, ADRA1A, and KCNMA1; the StarBase database verification results show that ADRA1A, ANGPTL1, FBXO32, KCNMA1, and DCN are downregulated in endometrial cancer tissues; LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 are upregulated in endometrial cancer; the constructed lncRNA-miRNA-hub Top10 mRNA network map identified CTD-2314B22, RP11-89 K21/hsa-miR-143, hsa-miR-424/LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 signal axis; survival analysis results show that CTD-2314B22, RP11-89 K21, hsa-miR-96, hsa-miR-211, LHX3, ST8SIA3, and DCN are all related to survival; RT-qPCR results indicate CTD-2314B22, RP11-89 K21, LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 are upregulated in endometrial cancer cells, and hsa-miR-143 and hsa-miR-424 are downregulated in endometrial cancer cells. Conclusion. From the perspective of the lncRNA-miRNA-mRNA network, our study identified CTD-2314B22, RP11-89 K21/hsa-miR-143, hsa-miR-424/LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 signal axis, which can present considerably potent biomarkers and therapeutic targets for treating endometrial cancer.

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Section: Discussionmentioning

confidence: 99%

Construction of Endometrial Carcinoma ceRNA Network and Screening of Key Genes Based on TCGA Database

Song

Chu

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Increasing evidence has demonstrated that the effects and mechanisms of lncRNAs on the initiation and development may be through network regulation and signaling pathways. 30 , 31 Thus, we further identified the target genes that were involved in the biological function and pathways. Targeted genes were mainly involved in the regulation of mRNA metabolic process and RNA stability, mRNA binding, and RNA localization.…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNAs in the Prediction of Survival of Patients with Digestive Cancers

Zhao¹,

Zhou²

2023

Turk J Gastroenterol

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Background: Long noncoding RNAs have been known to be involved in various cancers. This study aimed to find a long noncoding RNA signature to predict the prognostic risk of patients with digestive cancers, including esophageal carcinoma, stomach adenocarcinoma, liver hepatocellular carcinoma, and pancreatic adenocarcinoma. Methods: After screening differentially expressed long noncoding RNAs in 4 digestive cancers from The Cancer Genome Atlas database, the prognostic significance of the above differentially expressed long noncoding RNAs was evaluated by Kaplan–Meier analysis. Target genes of the corresponding differentially expressed long noncoding RNAs were predicted by StarBase. We performed bioinformatics methods, including gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, to explore the role and molecular mechanisms of differentially expressed long noncoding RNAs and predicted target genes in tumor progression. Results: A total of 4 differentially expressed long noncoding RNAs (AC093895.1, CASC9, LINC01980, and HOXC-AS2) with a significant prognostic value were identified. Moreover, 6 target genes were obtained. Also, functional enrichment analysis showed that these 4 DELs were mainly related to the regulation of mRNA metabolic process, regulation of RNA stability, mRNA binding, RNA localization, and spliceosome. Conclusion: The prognostic differentially expressed long noncoding RNAs and target genes in the digestive cancers were obtained, which may provide a novel direction for treatment and prognosis improvement of digestive cancers.

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“…Endometrial carcinoma (EC) is one of the most common malignant tumors in the female reproductive system. 1 In recent years, the incidence and mortality rates of EC have been increasing due to the changes in lifestyle. EC is divided into type I (estrogen-dependent) and type II (estrogen independent) according to the clinical and endocrine characteristics.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-133b Inhibits nTumor Cell Proliferation, Migration and Invasion by Targeting SUMO1 in Endometrial Carcinoma

Liao

Chen

Zhou

et al. 2021

Technol Cancer Res Treat

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Objectives: An increasing number of studies have confirmed that microRNAs (miRNAs/miRs), as oncogenes or tumor suppressor genes, play an important regulatory role in the occurrence and development of numerous types of cancer. The aim of the present study was to investigate the potential role and mechanism of miR-133b and small ubiquitin like modifier 1 (SUMO1) in the development of endometrial carcinoma (EC). Methods: First, Venn diagrams are used to identify the differential expressions of miRNAs in EC from GSE35794 and GSE25405 datasets. Next, we conduct a series of functional tests, including Cell Counting Kit-8, wound healing, and transwell and matrigel assays. Then, a bioinformatics tool, is used to identify downstream target genes of miR-133b and to verify the predicted results by RT-qPCR, Western blotting and double luciferase reporter gene analysis. Finally, in order to further study whether the cellular function of miR-133b is mediated by the expression of SUMO1, rescue experiments were carried out. Results: The results of bioinformatics studies showed that the expression of miR-133b was down-regulated in EC tissues, and the expression level of miR-133b was lower in patients with high grade, different histology or menopausal status. The results of functional assay showed that overexpression of miR-133b reduced cell proliferation, migration and invasion. On the contrary, miR-133b silence has the opposite effect. SUMO1 was the direct target of miR-133b and was negatively regulated by miR-133b. The decrease of SUMO1mRNA expression inhibited the proliferation, migration and invasion of EC cells, and reversed the effect of miR-133b on EC cells. Conclusion: The findings from the present study suggested that miR-133b may be a tumor suppressor gene and a potential therapeutic target for the treatment of EC.

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Identification of long noncoding RNA RP11-89K21.1 and RP11-357H14.17 as prognostic signature of endometrial carcinoma via integrated bioinformatics analysis

Cited by 4 publications

References 46 publications

Construction of Endometrial Carcinoma ceRNA Network and Screening of Key Genes Based on TCGA Database

Construction of Endometrial Carcinoma ceRNA Network and Screening of Key Genes Based on TCGA Database

Long Noncoding RNAs in the Prediction of Survival of Patients with Digestive Cancers

MicroRNA-133b Inhibits nTumor Cell Proliferation, Migration and Invasion by Targeting SUMO1 in Endometrial Carcinoma

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