BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Objective To analyze the age difference of gram negative isolates(GNB)from blood culture and antibiotic resistance profile between children and adults. Methods Age difference of pathogen distribution of GNB isolated from blood culture during 2015-2017 were retrospectively analyzed. WHONET 5.6 and Graphpad Prism 6 were used to perform Chi-square test on the pathogen proportion and antibiotic resistance rate. Results A total of 20 145 bacterial strains were isolated in Chongqing from 2015 to 2017. The top three strains of GNB were E. coli(56.7％, 6 688/11 799), K. pneumoniae(19.6％, 2 308/11 799), and P. aeruginosa(4.4％, 522/11 799). The resistant rate of E. coli to carbapenems was less than 1％. The resistant rate of K. pneumoniae to carbapenems was about 5％, while the resistant rate of S. marcescens was approximately 9％, similar to E. cloacae. The overall resistance rates of E. coli from adult patients to most antiobiotic agents were significantly higher than those of children, but the overall resistance rate of K. pneumoniae from children was higher than those of adults. The drug resistance rate of A. baumannii was higher than P. aeruginosa. A. baumannii isolates from adult patients were highly resistant to all drugs tested and more resistant than those from pediatric patients. Conclusions Majority of GNB strains isolated from blood culture were E. coli and K. pneumoniae, for which carbapenems are still active. More attention should be paid to carbapenem-resistant K. pneumoniae from children and A. baumannii from adults. National surveillance of nosocomial bloodstream infection should be highly evaluated.