CircTMEM59 Serves as miR-410-3p Sponge to Inhibit the Proliferation and Metastasis of Colorectal Cancer by Regulating HOXD8

Abstract

Circular RNAs (circRNAs) have been confirmed to be involved in the regulation of malignant progression of colorectal cancer (CRC). Our research aims to explore the role and mechanism of circTMEM59 (hsa_circ_0012634) in CRC progression. The expression of circTMEM59, miR-410-3p and Homeobox D8 (HOXD8) was measured by quantitative real-time PCR. Cell proliferation, migration and invasion were assessed by EdU assay, colony formation assay, wound healing assay and transwell assay. Marker protein expression was evaluated by western blot analysis. In addition, RNA interaction was confirmed by dual-luciferase reporter assay, RIP assay and RNA pull-down assay. CircTMEM59 was lowly expressed in CRC tumor tissues and cells. Upregulation of circTMEM59 repressed CRC cell proliferation, migration and invasion. MiR-410-3p could be sponged by circTMEM59, and its mimic also reversed the inhibition effect of circTMEM59 on CRC cell proliferation and metastasis. Also, HOXD8 was targeted by miR-410-3p, and its knockdown abolished the negative regulation of miR-410-3p inhibitor on CRC cell proliferation and metastasis. Furthermore, circTMEM59 inhibited CRC tumor growth by overexpressing HOXD8 through sponging miR-410-3p. In summary, our results demonstrated that circTMEM59 participated in the regulation of CRC progression through the miR-410-3p/HOXD8 axis, showing that circTMEM59 might be a potential target for the treatment of CRC.

Keywords: Colorectal cancer; HOXD8; circTMEM59; miR-410-3p.