Hsa_circ_0017639 expression promotes gastric cancer proliferation and metastasis by sponging miR-224-5p and upregulating USP3

Abstract

Gastric cancer (GC) is a common malignant tumor having poor prognosis globally. Circular RNA (circRNA) is a circular endogenous RNA generated by special selective splicing that occurs in various traits. Studies show that hsa_circ_0017639 is abnormally expressed and involved in tumorigenesis. Nevertheless, the hsa_circ_0017639 role in GC is unknown. This study detected hsa_circ_0017639 expression in a GC cell line using RT-qPCR. Subcellular localization of hsa_circ_0017639 was verified via FISH. We assessed correlations amongst miRNA, hsa_circ_0017639 and relative protein levels using luciferase reporter assays and RNA pulldown assays. The data illustrated that in hsa_circ_assays, expression was enhanced in GC cell. Downregulation of hsa_circ_0017639 decreased GC cell proliferation and migration in in vitro and in vivo experiments. RNA pulldown and RT-qPCR analysis verified that hsa_circ_0017639 sponged miR-224-5p. Bioinformatic and luciferase reporter assays validated that miR-224-5p and USP3 were downstream targets of hsa_circ_0017639. Upregulation of USP3 or downregulation of miR-224-5p restored proliferation and migration by MKN-28 and MGC-803 cells after hsa_circ_0017639 silencing. Upregulation of USP3 restored MKN-28 and MGC-803 cell proliferation and migration after overexpression of miR-224-5p. Our collective findings advised that hsa_circ_0017639 takes part in GC progression through regulating the miR-224-5p/USP3 axis, highlighting its potential as an effective GC therapeutic target.

Keywords: Gastric cancer; Hsa_circ_0017639; Sponge; USP3; miR-224-5p.