Background: Long noncoding RNAs (lncRNAs) can serve as a competing endogenous RNA (ceRNA) in regulating gene expression in multiple cancers by sponging miRNA. However, this mechanism is poorly studied in pancreatic cancer. This study aims to identify functional lncRNAs and their potential regulatory mechanisms in pancreatic cancer.
Methods: Differentially expressed lncRNA (DE-lncRNA), miRNA (DE-miRNA) and mRNA (DE-mRNA) were analyzed using data from three datasets (GSE89139, GSE24279 and GSE62452) from the Gene Expression Omnibus (GEO). The lncRNA-miRNA-mRNA interactions were predicted using miRcode and Targetscan. Gene ontology (GO) and pathway analysis of DE-mRNAs were performed using clusterProfiler. Survival analysis was conducted using data from The Cancer Genome Atlas (TCGA) database.
Results: Three hundred sixty-six DE-lncRNAs, 28 DE-miRNAs and 330 DE-mRNAs from pancreatic cancer and adjacent tissue were identified. A ceRNA network including 75 DE-lncRNAs, 18 DE-miRNAs and 85 DE-mRNAs was constructed, among which 16 DE-lncRNAs were associated with overall survival and 13 DE-lncRNAs were correlated with tumor progression. Three functional lncRNAs, GABPB1-AS1, ST7-AS1 and PSMG3-AS1, were identified as key functional lncRNAs, and their differential expression and potential ceRNA regulatory mechanism were validated by qPCR using pancreatic cancer cell lines and tissues.
Conclusions: Our study identifies novel lncRNAs associated with progression and prognosis of pancreatic cancer and contributes to better understanding of lncRNA-associated ceRNA regulatory mechanisms in pancreatic cancer.
Keywords: Pancreatic cancer; biomarker; competing endogenous RNA (ceRNA); long noncoding RNA (lncRNA); prognosis.
2020 Translational Cancer Research. All rights reserved.