DUB3 contributes to colorectal cancer cell migration and angiogenesis via NF-κB/HIF-1α

Abstract

Colorectal cancer (CRC) is a common malignancy with poor prognosis. This study aimed to explore the role of deubiquitinase 3 (DUB3) in CRC cell migration and angiogenesis as well as its molecular mechanism. HCT116 cells were transfected with DUB3 or EZH2 siRNA, or vectors overexpressing EZH2/HIF-1α. CCK8 and colony formation assay were used to assess cell proliferation; wound healing assay and Transwell assay were performed to determine cell migration and invasion; angiogenesis in CRC was detected using tube formation assay; WB was used to measure the protein levels of DUB3, EZH2, p65, p-p65, and HIF-1α. DUB3 downregulation inhibited proliferation, migration, invasion, and angiogenesis in CRC cells. Moreover, DUB3 could positively regulate NF-κB/HIF-1α pathway through EZH2. Overexpression of HIF-1α reversed the effects of DUB3 knockdown on CRC cell proliferation, migration, invasion, and angiogenesis. DUB3 contributes to CRC metastasis and angiogenesis by regulating NF-κB/HIF-1α pathway via EZH2, which may indicate a novel insight for the pathogenesis of CRC.