Tumor suppressor circPDE4D inhibits the progression of colorectal cancer and regulates oxaliplatin chemoresistance

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide, and it frequently develops resistance to chemotherapy. It was discovered that circular RNAs, which function as microRNA sponges, are involved in the pathogenesis of many cancers. This study aimed to investigate the biological functions of a circRNA derived from phosphodiesterase 4D (circPDE4D, hsa_circ_0072568) and its potential mechanism in oxaliplatin-resistant CRC. CircPDE4D expression were validated in human CRC cell lines and tissues. CircPDE4D siRNAs (si-circPDE4D) and LV003-circPDE4D plasmid were applied to investigate the function of circPDE4D. A quantitative real-time polymerase chain reaction was used to detect the levels of circPDE4D, its predicted sponge miRNAs, and their target genes. Cell proliferation was assessed by MTS（3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)–2H-tetrazolium） assay. Cell migration and invasion capacity were evaluated by transwell assay. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was used to stain apoptotic cells. The results showed that circPDE4D expression was downregulated in CRC cells and tissues. Transfection with si-circPDE4D promoted cell proliferation, migration, and invasion, and inhibited apoptosis in DLD1 cells. Transfection with LV003-circPDE4D showed the opposite effect. Besides, circPDE4D presented higher expression in HCT116/L cells than that in HCT116 cells. Si-circPDE4D or lv003-circPDE4D transfection increased or decreased cell proliferationin in both two cells. Moreover, si-circPDE4D transfection inhibited cell apoptosis, while LV003-circPDE4D induced apoptosis in HCT116/L cells. LV003-CircPDE4D reduced hsa-miR-569 expression while increasing SPI1 expression in HCT116/L. CircPDE4D could inhibit tumorigenesis and progression of both CRC and oxaliplatin-resistant CRC, providing insight for the development of therapeutic strategies.