Proteomic profiling identifies novel inflammation-related plasma proteins associated with ischemic stroke outcome.

BACKGROUND: The inflammatory response to cerebral ischemia is complex; however, most clinical studies of stroke outcome focus on a few selected proteins. We, therefore, aimed to profile a broad range of inflammation-related proteins to: identify proteins associated with ischemic stroke outcome that are independent of established clinical predictors; identify proteins subsets for outcome prediction; and perform sex and etiological subtype stratified analyses. METHODS: Acute-phase plasma levels of 65 inflammation-related proteins were measured in 534 ischemic stroke cases. Logistic regression was used to estimate associations to unfavorable 3-month functional outcome (modified Rankin Scale score > 2) and LASSO regressions to identify proteins with independent effects. RESULTS: Twenty proteins were associated with outcome in univariable models after correction for multiple testing (FDR < 0.05), and for 5 the association was independent of clinical variables, including stroke severity (TNFSF14 [LIGHT], OSM, SIRT2, STAMBP, and 4E-BP1). LASSO identified 9 proteins that could best separate favorable and unfavorable outcome with a predicted diagnostic accuracy (AUC) of 0.81; three associated with favorable (CCL25, TRAIL [TNFSF10], and Flt3L) and 6 with unfavorable outcome (CSF-1, EN-RAGE [S100A12], HGF, IL-6, OSM, and TNFSF14). Finally, we identified sex- and etiologic subtype-specific associations with the best discriminative ability achieved for cardioembolic, followed by cryptogenic stroke. CONCLUSIONS: We identified candidate blood-based protein biomarkers for post-stroke functional outcome involved in, e.g., NLRP3 inflammasome regulation and signaling pathways, such as TNF, JAK/STAT, MAPK, and NF-κB. These proteins warrant further study for stroke outcome prediction as well as investigations into the putative causal role for stroke outcome.

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

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.

STAMBPL1 knockdown has antitumour effects on gastric cancer biological activities.

The present study aimed to investigate the effects and mechanisms of STAM binding protein-like 1 (STAMBPL1) knockdown in the suppression of gastric cancer activities. Pathological data and STAMBPL1 protein expression were analysed in 36 patients with gastric cancer, including 24 stage I-II and 12 stage III-IV patients, by haematoxylin and eosin staining and immunohistochemistry. In vitro cell experiments were performed to measure AGS cell proliferation, apoptosis, invasion and migration by MTT, Celigo cell count, flow cytometry, Transwell and wound healing assays following STAMBPL1 knockdown. The relative protein expression levels were evaluated by western blotting. When compared with the adjacent normal tissues, STAMBPL1 protein expression in the gastric cancer tissues with increasing stages was significantly upregulated (P<0.01 or P<0.001). STAMBPL1 gene expression was not identified to be significantly different between AGS and MGC80-3 gastric cancer cells (P>0.05). Following STAMBPL1 knockdown by short hairpin RNA (sh)STAMBPL1, cell proliferation was significantly suppressed, the cell apoptosis rate was significantly upregulated, and the numbers of invasive AGS cells and the AGS wound healing rate were significantly decreased (P<0.01 and P<0.001, respectively), compared with those in the shControl group. Additionally, STAMBPL1 and NF-κB protein expression levels were significantly downregulated in the shSTAMBPL1 group (P<0.001, respectively). STAMBPL1 may be oncogenic in gastric cancer, and STAMBPL1 knockdown may suppress gastric cancer development.