Identification of lncRNAs and Their Functional Network Associated with Chemoresistance in SW1990/GZ Pancreatic Cancer Cells by RNA Sequencing

摘要

Drug resistance is a major problem in the treatment of pancreatic cancer (PC). Long noncoding (lnc) RNAs modulate a variety of cellular processes. This study was carried out to identify lncRNAs that are differentially expressed in drug-resistant PC by next-generation RNA sequencing. We identified 205 differentially expressed lncRNAs (DELs) and 847 differentially expressed mRNAs (DEMs) in a comparison of gemcitabine-resistant and-sensitive SW1990 human PC cells. The expression levels of 12 randomly selected lncRNAs were confirmed by quantitative real-time PCR. A total of 55 and 99 DEMs were predicted to be targeted by the DELs through cis and trans mechanisms, respectively. The DEMs were significantly enriched in the Gene Ontology terms cell part, binding, and cellular processes, and a Kyoto Encyclopedia of Genes and Genomes analysis showed that they were associated with metabolic pathway, pathways in cancer, insulin resistance, microRNAs in cancer, and phosphotidylinositol 3-kinase-Akt signaling pathway. A coexpression network revealed a hub comprising lncRNAs (MIR210HG, SNHG1, and LOC729970) and mRNAs (RAB3D, DDX17, and SPNS2) that presumably mediate drug resistance in PC. The identified lncRNAs can serve as diagnostic or prognostic biomarkers and therapeutic targets for PC.