High-throughput sequencing of circRNAs reveals novel insights into mechanisms of nigericin in pancreatic cancer.

Background: Our previous study had proved that nigericin could reduce colorectal cancer cell proliferation in dose- and time-dependent manners by targeting Wnt/β-catenin signaling. To better elucidate its potential anti-cancer mechanism, two pancreatic cancer (PC) cell lines were exposed to increasing concentrations of nigericin for different time periods, and the high-throughput sequencing was performed to explore the circRNA expression profiles after nigericin exposure on pancreatic cancer (PC) cells.

Results: In this study, a total of 183 common differentially expressed circRNAs were identified, and the reliability and validity of the sequencing data were verified by the PCR analysis. According to the parental genes of circRNAs, the GO analysis was performed to predict the most enriched terms in the biological process, cellular components and molecular functions. The KEGG analysis and pathway-pathway network exhibited the potential signal pathways and their regulatory relationships. Meanwhile, a potential competing endogenous RNA (ceRNA) mechanism through a circRNA-miRNA-mRNA network was applied to annotate potential functions of these common differentially expressed circRNAs, and these predicted miRNAs or mRNAs might be involved in nigericin damage.

Conclusions: By the bioinformatics method, our data will facilitate the understanding of nigericin in PC cells, and provide new insight into the molecular mechanism of nigericin toward cancer cells. This is the first report that discusses the potential functions of nigericin in cancers through the bioinformatics method. Our data will facilitate the understanding of nigericin-mediated anti-cancer mechanisms in PC.