STAM binding protein regulated by hsa_circ_0007334 exerts oncogenic potential in pancreatic cancer

Abstract

Background: Pancreatic cancer (PC) is a highly aggressive and metastatic malignancy. The molecular events related to PC have not yet been fully elucidated. The STAM binding protein (STAMBP), a deubiquitinase, contributes to carcinogenesis in several types of cancer. Our study aims to investigate the function of STAMBP in the progression of PC. Methods: Fifteen pairs of tumor and tumor-adjacent tissues were obtained from PC patients. Human pancreatic cancer cell lines, SW 1990 and BxPC-3, were transfected with short hairpin RNA targeting STAMBP or/and vectors overexpressing wild-type STAMBP or STAMBP D348A mutants (inactive mutants of STAMBP). SW 1990 cells were co-transfected with vectors overexpressing STAMBP and small interfering RNA targeting hsa_circ_0007334. Results: STAMBP was overexpressed in the tumor tissues as compared with the tumor-adjacent tissues from PC patients. Higher STAMBP expression in the tumor tissues showed worse prognosis. Loss/gain-of-function experiments revealed that STAMBP promoted the malignant behaviors of PC cells in vitro and xenograft tumor growth in vivo. Activation of NF-κB in PC cells was triggered by STAMBP. However, inactive mutants of STAMBP lost these biological functions in PC. hsa_circ_0007334, an oncogene in PC progression, was found to up-regulate STAMBP expression in PC cells. STAMBP up-regulation reversed the effects of hsa_circ_0007334 silencing on cell mobility. Conclusions: These results indicated that STAMBP depended on its deubiquitinase activities to induce the malignant behaviors of PC cells and was involved in the regulatory mechanism of hsa_circ_0007334 on PC cell mobility. Our findings provide a novel insight into the molecular mechanism of PC.