Circular RNA CirCHIPK3 promotes cell proliferation and invasion of breast cancer by sponging miR-193a/HMGB1/PI3K/AKT axis.

Abstract

BackgroundThe aim of this study was to explore the potential mechanism of circular RNA (circRNA) CirCHIPK3 on the malignant proliferation and metastasis of breast cancer (BC).MethodsHuman BC samples and their matched normal adjacent tissues were obtained from 50 patients to assess the expression of CirCHIPK3 and its relationship with BC prognosis. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of CirCHIPK3 in BC progression and its underlying molecular mechanisms. Moreover, the interaction of CirCHIPK3, miR‐193a, and HMGB1 was examined using bioinformatics, FISH, RIP, RNA‐pull down and luciferase reporter assays. Western blot analysis was performed to examine the expression of HMGB1, p‐PI3K, total PI3K, p‐AKT, and AKT after si‐CirCHIPK3 transfection.ResultsUpregulation of CirCHIPK3 was identified in BC, which predicted a worse prognosis in BC patients. Furthermore, it was found that CirCHIPK3 facilitated cell proliferation, migration, and invasion in BC by regulating miR‐193a/HMGB1/PI3K/AKT signaling. CirCHIPK3 acted as a sponge for miR‐193a to facilitate HMGB1 expression. si‐CirCHIPK3 also inhibited tumor growth of BC in nude mice. si‐CircCHIPK3 decreased HMGB1/PI3K/AKT signal expression in MDA‐MB‐231 cells, whereas overexpression of CircCHIPK3 enhanced HMGB1/PI3K/AKT signal.ConclusionsCirCHIPK3 regulated miR‐193a/HMGB1/PI3K/AKT signaling to facilitate BC development and progression, providing a novel therapeutic target for BC.