Hsa_circ_0079662 induces the resistance mechanism of the chemotherapy drug oxaliplatin through the TNF-α pathway in human colon cancer

Abstract

The aim of the study was to research the biological functions of circRNA (hsa_circ_0079662) and its underlying mechanism in colorectal cancer. Drug-resistant cell lines (HT29-LOHP, HCT116-LOHP, HCT8-LOHP) were separately dealt with oxaliplatin concentration gradient (0.1-10 μmol/L). Real-time PCR, Western blotting, dual-luciferase assay, miRNA pull-down assay, coimmunoprecipitation and ELASA were performed to explore the mechanism of chemotherapy drug oxaliplatin resistance in CRC. The results showed that the expression of hsa_circ_0079662 was increased in drug-resistant cell lines by RT-PCR. The expression of HOXA9, TRIP6, Vcam-1, VEGFC, MMP3, MMP9 and MMP14 was higher by Western blotting. Interaction between HOXA9 and TRIP6 in CO-IP detection. Additionally, the cytokines TNF-α, IL-1 and IL-6 were also found. In conclusion, hsa_circ_0079662, as a ceRNA binding with hsa-mir-324-5p, can regulate target gene HOXA9 and induced the mechanism of chemotherapy drug oxaliplatin resistance in CRC through the TNF-α pathway in human colon cancer.

Keywords: HOXA9; Hsa_circ_0079662; TNF-α pathway; ceRNA; colorectal cancer.