ABSTRACT
BACKGROUND: Colorectal cancer (CRC) is one of the most lethal malignancies. Tripartite Motif Containing 14 (TRIM14) is a member of TRIM family proteins, which are involved in the pathogenesis of various cancers. This study aimed to investigate TRIM14 expression in CRC tissues, and its effects on the migration and invasion of CRC cell lines. METHODS: TRIM14 mRNA expression was detected by real-time PCR analysis. Cell migration and invasion were measured by Transwell assays. Protein expression was assessed by western blot analysis. RESULTS: The expression of TRIM14 was significantly higher in CRC tissues than in matched non-cancerous tissues. TRIM14 knockdown by specific short hairpin RNA (shRNA) attenuated CRC cell migration and invasion, whereas TRIM14 overexpression caused reverse effect. Moreover, TRIM14 positively regulated the protein levels of sphingosine kinase 1 (SPHK1) and phosphorylated STAT3 (p-STAT3), as well as the mRNA and protein expression of matrix metalloproteinase 2, MMP9 and vascular endothelial growth factor, which are transcriptional targets of the STAT3 signaling pathway. Importantly, the blockage of the SPHK1/STAT3 signaling pathway by SKI-II or AG490 could reverse the TRIM14-promoted CRC cell migration and invasion. CONCLUSIONS: Our results reveal a critical role for TRIM14 in promoting migration and invasion of CRC cells, and suggest TRIM14 may serve as a potential molecular target to prevent CRC metastasis.
ABSTRACT
BACKGROUND: CXC chemokine ligand-12 (CXCL12) is released during brain injury. The objective of this study was to investigate relationship between serum CXCL12 concentration, mortality and trauma severity in patients with traumatic brain injury (TBI). METHODS: We determined serum CXCL12 concentration of 132 controls and 132 patients with severe TBI. Trauma severity was assessed using Glasgow Coma Scale (GCS) score. The end-point of the study was 30-day mortality. RESULTS: Serum CXCL12 concentration were significantly higher in the patients than in the controls (13.3±6.8 vs. 1.5±0.5 ng/ml, P<0.001). There was a negative correlation between CXCL12 concentration and GCS scores (r=-0.588, P<0.001). The optimal cutoff value of CXCL12 as a mortality indicator was estimated to be 15.4 ng/ml, which yielded a sensitivity of 71.0% and a specificity of 72.2%, with the area under curve at 0.808 [95% confidence (CI), 0.730-0.871]. Serum CXCL12 concentration>19.5 ng/ml were associated independently with 30-day mortality (odds ratio, 6.951; 95% CI, 2.027-18.477; P<0.001) and 30-day overall survival (hazard ratio, 4.398; 95% CI, 2.088-15.286; P<0.001). CONCLUSIONS: Increased serum CXCL12 concentration is associated highly with trauma severity and mortality following TBI.
