BackgroundTo investigate the effect of CXCL12 gene silencing on proliferation,invasion, angiogenesis and the relationship of MAPK/PI3K/AP-1 signaling pathway in colon cancer cells.MethodsRT-PCR and Western-blot were used to detect the expression of CXCL12 mRNA and protein in four colon cancer cell lines. Human colon cancer cells were transfected with CXCL12 siRNA carrying by Lipofectamine 2000. The expression of CXCL12 protein was confirmed by immunoblotting. WST-1, invasion and angiogenesis assay were used to examine the effect on proliferation, invasion and angiogenesis in colon cancer cells after CXCL12 siRNA silence, respectively. The phosphorylation of MAPK/PI3K/AP-1 protein levels was detected by Western blotting in CXCL12 siRNA suppression DLD-1 cell.ResultsCXCL12 mRNA and proteins were only expressed in DLD-1 colon cancer cell lines. CXCL12 siRNA were transfected into DLD-1 cells, the expression CXCL12 proteins was significantly inhibited (P < 0.01), and the proliferation, invasion and angiogenesis of DLD-1 cells were inhibited significantly (P < 0.01). CXCL12 gene silencing resulted in blockage of MAPK, PI3K and AP-1 phosphorylation by CXCL12-induced in DLD-1 colon cancer cell.ConclusionThe silencing CXCL12 gene significantly inhibits the proliferation, invasion and angiogenesis ability of some types colon carcinoma cells through down-regulation of MAPK/PI3K/AP-1 signaling pathway.

Background: Clear cell renal cell carcinoma (ccRCC), as the commonest type among renal cell cancers, is featured with easy relapse and metastasis. Despite mounting achievements on its treatment and diagnosis, the identification of new biomarkers remains urgent. Purposes: Present study aimed to explore the role of microRNA-4429 (miR-4429) in ccRCC. Methods: The expression of miR-4429 and cyclin-dependent kinase 6 (CDK6) was evaluated by real-time polymerase chain reaction and Western blot. Cell proliferation, migration and invasion was evaluated by MTT and transwell assays. The interaction between miR-4429 and CDK6 was assessed by luciferase reporter assay. Prognostic significance of miR-4429 was evaluated by Kaplan-Meier analysis. Correlation between miR-4429 and CDK6 was determined by Spearman's correlation analysis. Results: Firstly, the downregulation of miR-4429 and upregulation of CDK6 in ccRCC tissues and cells were uncovered by quantitative real-time polymerase chain reaction. The prognostic significance of miR-4429 in ccRCC patients was proved by Kaplan-Meier analysis. Gain-and loss-of-function assays validated the suppressive effect of miR-4429 on cell proliferation, migration, invasion, as well as epithelial-mesenchymal transition (EMT) progression. The interaction between miR-4429 and CDK6 was predicted by bioinformatics tool and confirmed by luciferase reporter assay. And the negative expression correlation between miR-4429 and CDK6 was verified by Spearman's correlation analysis. Rescue assays confirmed the role of miR-4429/CDK6 in proliferation, metastasis and EMT progression in ccRCC. Conclusions: Present study revealed that miR-4429 suppressed ccRCC tumor progression and EMT by targeting CDK6.

Purpose To explore the association between circulating mononuclear cell mitochondrial DNA copy number and the prognosis of sepsis patients based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3 definition). Methods A total of 200 adult patients who had recently devoloped sepsis were prospectively recruited as the study cohort. Demographic and clinical data were recorded along with a 28-day outcome. Mononuclear cell mtDNA copy number was assessed by quantitative PCR. Results The 28-day outcome of sepsis patients was significantly associated with circulating mononuclear cell mtDNA copy number. The median mononuclear cell relative mtDNA copy number of survivors was significantly higher than that of nonsurvivors (406.68, range 196.65–625.35 vs. 320.57, range 175.98–437.33, p = 0.001). The Cox proportional hazard survival model analysis indicated that mononuclear cell relative mtDNA copy number was significantly negative associated with the 28-day outcome. For every additional unit of mononuclear cell mtDNA relative copy number, the risk of death falls by 0.1% (HR = 0.999, 95% CI = 0.998 to 1.000, p = 0.017). Conclusions Our data indicate first that circulating mononuclear cellular mtDNA copy number might be helpful for outcome predictions in sepsis patients, and second that lower mtDNA copy number implied poor prognosis.

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