Abstract 3016: Dicer overexpression contributes to chemoresistance in colorectal cancer via up-regulating a set of miRNAs

Abstract

Abstract Chemotherapy has a good success rate in the treatment of colorectal cancer; however, recurrence of colorectal cancer is still frequent due to acquired resistance. Aurora-A, a cell cycle-regulated kinase, plays an important role in colorectal cancer development and drug resistance. Dicer, one of the key enzymes of the microRNA (miRNA) biogenesis pathway, may be involved in chemoresistance through regulating the expression of miRNAs. According to the TCGA database, the expression levels of Dicer and Aurora-A were increased in colorectal cancer, which may contribute to chemoresistance. Our results showed that the protein levels of Dicer and Aurora-A are increased in oxaliplatin resistant cell lines. Knocked-down expression of Dicer or Aurora-A can enhance drug sensitivity in oxaliplatin-resistant cells; in contrast, overexpression of Dicer or Aurora-A increased drug resistance in parental drug sensitive cells. By next-generation sequencing, we found that the expression of a set of miRNAs is increased in oxaliplatin resistant cells. Dicer overexpression enhances the expression of those miRNAs in drug sensitive parental cells. Clinical evaluation further confirmed the increased expression of those miRNA in the plasma of CRC patients with a poor response to oxaliplatin. Our results suggest that those miRNAs may act as biomarkers to predict oxaliplatin response in colorectal cancer by detecting their plasma miRNAs. The molecular mechanism of those miRNAs in regulating the drug response is currently under our investigation. Citation Format: Li Jyuan Lin, Liang-Yi Hung. Dicer overexpression contributes to chemoresistance in colorectal cancer via up-regulating a set of miRNAs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3016.