Dataset Information

A putative competing endogenous RNA network in cisplatin-resistant lung adenocarcinoma cells identifying potentially rewarding research targets.

ABSTRACT: Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer and has a poor 5 year survival rate (<10%). Cisplatin is one of the most effective chemotherapeutic treatments for LUAD, even though it is of limited overall utility due to acquired drug resistance. To identify possible genetic targets for the mitigation of cisplatin resistance, gene expression data from cisplatin-resistant cell lines were integrated with patient information. Expression data for cisplatin-resistant and cisplatin-sensitive A549 cell lines were obtained from the Gene Expression Omnibus database, while LUAD patient data was obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs (DEmRNAs), microRNAs (DEmiRNAs) and long non-coding RNAs (DElncRNAs) were identified between the cisplatin-sensitive and cisplatin-resistant cells. Using the TCGA patient data, 33 DEmRNAs associated with survival were identified. A total of 74 DElncRNAs co-expressed with the survival-associated DEmRNAs, and 11 DEmiRNAs that regulated the survival-associated DEmRNAs, were also identified. A competing endogenous RNA (ceRNA) network was constructed based on the aforementioned results, which included 17 survival-associated DEmRNAs, 9 DEmiRNAs and 16 DElncRNAs. This network revealed 8 ceRNA pathway axes possibly associated with cisplatin resistance in A549 cells. Specifically, the network suggested that the lncRNAs HOXD-AS2, LINC01123 and FIRRE may act as ceRNAs to increase cisplatin resistance in human LUAD cells. Therefore, it was speculated that these lncRNAs represent potentially rewarding research targets.

SUBMITTER: Li Y

PROVIDER: S-EPMC7202328 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A putative competing endogenous RNA network in cisplatin-resistant lung adenocarcinoma cells identifying potentially rewarding research targets.

Li Yepeng Y Huang Shiqing S Wei Zhongheng Z Yang Bo B

Oncology letters 20200327 6

Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer and has a poor 5 year survival rate (<10%). Cisplatin is one of the most effective chemotherapeutic treatments for LUAD, even though it is of limited overall utility due to acquired drug resistance. To identify possible genetic targets for the mitigation of cisplatin resistance, gene expression data from cisplatin-resistant cell lines were integrated with patient information. Expression data for cisplatin-resistant ...[more]

PMID: 32382346

Similar Datasets

Project description:Increasing evidence has shown competitive endogenous RNAs (ceRNAs) play key roles in numerous cancers. Nevertheless, the ceRNA network that can predict the prognosis of lung adenocarcinoma (LUAD) is still lacking. The aim of the present study was to identify the prognostic value of key ceRNAs in lung tumorigenesis. Differentially expressed (DE) RNAs were identified between LUAD and adjacent normal samples by limma package in R using The Cancer Genome Atlas database (TCGA). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway function enrichment analysis was performed using the clusterProfiler package in R. Subsequently, the LUAD ceRNA network was established in three steps based on ceRNA hypothesis. Hub RNAs were identified using degree analysis methods based on Cytoscape plugin cytoHubba. Multivariate Cox regression analysis was implemented to calculate the risk score using the candidate ceRNAs and overall survival information. The survival differences between the high-risk and low-risk ceRNA groups were determined by the Kaplan-Meier and log-rank test using survival and survminer package in R. A total of 2,989 mRNAs, 185 lncRNAs, and 153 miRNAs were identified. GO and KEGG pathway function enrichment analysis showed that DE mRNAs were mainly associated with "sister chromatid segregation," "regulation of angiogenesis," "cell adhesion molecules (CAMs)," "cell cycle," and "ECM-receptor interaction." LUAD-related ceRNA network was constructed, which comprised of 54 nodes and 78 edges. Top ten hub RNAs (hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-340-5p, hsa-miR-377-3p, hsa-miR-21-5p, hsa-miR-326, SNHG1, RALGPS2, and PITX2) were identified according to their degree. Kaplan-Meier survival analyses demonstrated that hsa-miR-21-5p and RALGPS2 had a significant prognostic value. Finally, we found that a high risk of three novel ceRNA interactions (SNHG1-hsa-miR-21-5p-RALGPS2, SNHG1-hsa-miR-326-RALGPS2, and SNHG1-hsa-miR-377-3p-RALGPS2) was positively associated with worse prognosis. Three novel ceRNAs (SNHG1-hsa-miR-21-5p-RALGPS2, SNHG1-hsa-miR-326-RALGPS2, and SNHG1-hsa-miR-377-3p-RALGPS2) might be potential biomarkers for the prognosis and treatment of LUAD.

Project description:Evidence is increasingly indicating that circular RNAs (circRNAs) are closely involved in tumorigenesis and cancer progression. However, the function and application of circRNAs in lung adenocarcinoma (LUAD) are still unknown. In this study, we constructed a circRNA-associated competitive endogenous RNA (ceRNA) network to investigate the regulatory mechanism of LUAD procession and further constructed a prognostic signature to predict overall survival for LUAD patients. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were selected to construct the ceRNA network. Based on the TargetScan prediction tool and Pearson correlation coefficient, we constructed a circRNA-associated ceRNA network including 11 DEcircRNAs, 8 DEmiRNAs, and 49 DEmRNAs. GO and KEGG enrichment indicated that the ceRNA network might be involved in the regulation of GTPase activity and endothelial cell differentiation. After removing the discrete points, a PPI network containing 12 DEmRNAs was constructed. Univariate Cox regression analysis showed that three DEmRNAs were significantly associated with overall survival. Therefore, we constructed a three-gene prognostic signature for LUAD patients using the LASSO method in the TCGA-LUAD training cohort. By applying the signature, patients could be categorized into the high-risk or low-risk subgroups with significant survival differences (HR: 1.62, 95% CI: 1.12-2.35, log-rank p = 0.009). The prognostic performance was confirmed in an independent GEO cohort (GSE42127, HR: 2.59, 95% CI: 1.32-5.10, log-rank p = 0.004). Multivariate Cox regression analysis proved that the three-gene signature was an independent prognostic factor. Combining the three-gene signature with clinical characters, a nomogram was constructed. The primary and external verification C-indexes were 0.717 and 0.716, respectively. The calibration curves for the probability of 3- and 5-year OS showed significant agreement between nomogram predictions and actual observations. Our findings provided a deeper understanding of the circRNA-associated ceRNA regulatory mechanism in LUAD pathogenesis and further constructed a useful prognostic signature to guide personalized treatment of LUAD patients.

Dataset Information

A putative competing endogenous RNA network in cisplatin-resistant lung adenocarcinoma cells identifying potentially rewarding research targets.

Publications

A putative competing endogenous RNA network in cisplatin-resistant lung adenocarcinoma cells identifying potentially rewarding research targets.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets