Abstract 5890: Aurora-A potentiates chemoresistance via regulating the microRNA biogenesis pathway

Abstract

Abstract Chemotherapy has a good success rate in colorectal cancer; however, recurrence of colorectal cancer is still frequent due to the development of drug resistance. MicroRNA (miRNA) is a type of non-coding RNA with a size of around 19-22 nucleotides and plays an important role in regulating many biological functions, the onset of diseases, as well as drug response. It was reported that Dicer, one of the key enzymes of the miRNA biogenesis pathway, may be involved in the chemoresistance through regulating the expression of miRNAs. Aurora-A, a cell cycle-regulated kinase, plays a vital role in cancer development and chemoresistance. According to the TCGA database, the expression levels of Dicer and Aurora-A are both increased in colorectal cancer. Here, we demonstrated that overexpressed Aurora-A can regulate the chemodrug response by influencing the miRNA biogenesis pathway via Dicer in colorectal cancer. Our results showed that the protein level, but not the mRNA expression, of Dicer was decreased upon 5-FU or oxaliplatin treatment in drug sensitive cells; whereas, the expression level of Dicer was increased in oxaliplatin resistant cell lines. Knockdown expression of Dicer in oxaliplatin resistant cell lines could reverse the resistance of oxaliplatin. The expression levels of several potential miRNAs changed upon chemodrugs treatment. Interestingly, we found that overexpressed Aurora-A could increase the expression of Dicer and potentiate drug resistance in colorectal cancer cells. In contrast, knockdown expression of Aurora-A decreased Dicer protein expression and led to enhanced drug sensitivity. Taken together, our results suggested that Aurora-A and Dicer can collaborate to regulate drug response through influencing the miRNA biogenesis pathway in colorectal cancer. The further mechanism of Dicer and Aurora-A in chemoresistance is currently under our investigation. Citation Format: Li Jyuan Lin. Aurora-A potentiates chemoresistance via regulating the microRNA biogenesis pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5890.