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

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. 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. 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. 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.