Downregulation of miR-199b is associated with distant metastasis in colorectal cancer via activation of SIRT1 and inhibition of CREB/KISS1 signaling.

The progression of distant metastasis cascade is a multistep and complicated process, frequently leading to a poor prognosis in cancer patients. Recently, growing evidence has indicated that deregulation of microRNAs (miRNAs) contributes to tumorigenesis and tumor progression in colorectal cancer (CRC). In the present study, by comparing the miRNA expression profiles of CRC tissues and corresponding hepatic metastasis tissues, we established the downregulation of miR-199b in CRC metastasis tissues. The decrease in miR-199b expression was significantly correlated to late TNM stage and distant metastasis. Moreover, Kaplan-Meier curves showed that CRC patients with high expression level of miR-199b had a longer median survival. Functional assays results indicated that the restoration of miR-199b considerably reduced cell invasion and migration in vitro and in vivo, and increased the sensitivity to 5-FU and oxaliplatin. Further dual-luciferase reporter gene assays revealed that SIRT1 was the direct target of miR-199b in CRC. The expression of miR-199b was inversely correlated with SIRT1 in CRC specimens. SIRT1 knockdown produced effects on biological behavior that were similar to those of miR-199b overexpression. Furthermore, through Human Tumor Metastasis PCR Array we discovered KISS1 was one of the downstream targets of SIRT1. Silencing of SIRT1 upregulated KISS1 expression by enhancing the acetylation of the transcription factor CREB. The latter was further activated via binding to the promoter of KISS1 to induce transcription. Thus, we concluded that miR-199b regulates SIRT1/CREB/KISS1 signaling pathway and might serve as a prognosis marker or a novel therapeutic target for patients with CRC.

MicroRNA-217 functions as a prognosis predictor and inhibits colorectal cancer cell proliferation and invasion via an AEG-1 dependent mechanism.

BACKGROUND: Recent studies have indicated the possible function of miR-217 in tumorigenesis. However, the roles of miR-217 in colorectal cancer (CRC) are still largely unknown. METHODS: We examined the expression of miR-217 and AEG-1 in 50 CRC tissues and the corresponding noncancerous tissues by qRT-PCR. The clinical significance of miR-217 was analyzed. CRC cell lines with miR-217 upregulation and AEG-1 silencing were established and the effects on tumor growth in vitro and in vivo were assessed. Dual-luciferase reporter gene assays were also performed to investigate the interaction between miR-217 and AEG-1. RESULTS: Our data demonstrated that miR-217 was significantly downregulated in 50 pairs of colorectal cancer tissues. MiR-217 expression levels were closely correlated with tumor differentiation. Moreover, decreased miR-217 expression was also associated with shorter overall survival of CRC patients. MiR-217 overexpression significantly inhibited proliferation, colony formation and invasiveness of CRC cells by promoting apoptosis and G0/G1 phase arrest. Interestingly, ectopic miR-217 expression decreased AEG-1 expression and repressed luciferase reporter activity associated with the AEG-1 3'-untranslated region (UTR). AEG-1 silencing resulted in similar biological behavior changes to those associated with miR-217 overexpression. Finally, in a nude mouse xenografted tumor model, miR-217 overexpression significantly suppressed CRC cell growth. CONCLUSIONS: Our findings suggest that miR-217 has considerable value as a prognostic marker and potential therapeutic target in CRC.

MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by regulating the MAP4K4/c-Jun/MDM2 signaling pathway.

Tumor growth cascade is a complicated and multistep process with numerous obstacles. Until recently, evidences have shown the involvement of microRNAs (miRNAs) in tumorigenesis and tumor progression of various cancers, including colorectal cancer (CRC). In this study, we explored the role of miR-194 and its downstream pathway in CRC. We acquired data through miRNA microarray profiles, showing that the expression of miR-194 was significantly suppressed in CRC tissues compared with corresponding noncancerous tissues. Decreased miR-194 expression was obviously associated with tumor size and tumor differentiation, as well as TNM stage. Both Kaplan-Meier and multivariate survival analysis showed that downregulated miR-194 was associated with overall survival. Moreover, functional assays indicated that overexpression of miR-194 in CRC cell lines inhibited cell proliferation both in vitro and in vivo. In addition, using dual-luciferase reporter gene assay, we found MAP4K4 was the direct target of miR-194. Silencing of MAP4K4 resulted in similar biological behavior changes to that of overexpression of miR-194. We also observed through Human Gene Expression Array that MDM2 was one of the downstream targets of MAP4K4. Knockdown of MAP4K4 downregulated MDM2 expression through transcription factor c-Jun binding to the -1063 to -1057 bp of the promoter. These results suggest that miR-194, regulating the MAP4K4/c-Jun/MDM2 signaling pathway, might act as a tumor suppressor and serve as a novel target for CRC prevention and therapy.

[Surveillance of bacterial distribution and drug resistance in inpatients with surgical infections: a single center study].

OBJECTIVE: To investigate the bacterial distribution and drug resistance in patients with surgical infections, and provide the basis for the standardization treatment of the surgical infection. METHODS: Retrospectively analyzed from January 2008 to December 2011 surgical infection in our samples bacteria identification and drug sensitivity test results. RESULTS: A total of 3829 nonduplicate isolates from 3257 samples, Gram-negative bacteria accounted for 62.4% (the main microbes were P.aeruginosa, K. pneumonia and E.coli etc) and Gram-positive bacteria accounted for 37.6% (the main microbes were Enterococcus, Staphylococcus and coagulase negative Staphylococcus). Incidence of Staphylococcus aureus and Enterococcus faecalis were on an obvious increase. For the performance of the high level of sensitive to Imipenem, Amikacin, Piperacillin and Tazobactam by E. coli and K. pneumonia. The Pseudomonas aeruginosa and Acinetobacter baumannii to cephalosporins, Carbapenems and Fluoroqinolones were higher resistant with Multidrug resistance. No vancomycin and teicoplanin resistant Enterococcus faecium were found. The prevalence of ESBL E.coli was 45.6%-61.5% and ESBL K.pneumoniae isolates were fluctuated. The methicillin-resistant S.aureus (MRSA) isolates were relatively high (21.1%-55.8%), and methicillin-resistant Staphylococcus epidermidis was higher than the other Gram-positive cocci. Vancomycin for Staphylococcus performance was highly sensitive. CONCLUSIONS: The main composition of surgical clinical infection pathogens are Gram-negative bacillus, and the emergency of resistance of bacteria to antibacterial drugs is a common phenomenon. The resistant rate shows ascendant trend; Drug resistance is significantly higher in Pseudomonas aeruginosa and Acinetobacter baumannii. Antimicrobial resistance is a serious and challenging issue.

[Animal experimental study of biodegradable magnesium alloy stapler for gastrointestinal anastomosis].

OBJECTIVE: To explore the safety and feasibility of biodegradable magnesium alloy stapler based on the result of animal experimental study for gastrointestinal anastomosis. METHODS: Sixteen beagle dogs were equally and randomly divided into experimental (magnesium alloy) group and control (titanium alloy) group. A gastrojejunal and a colonic anastomosis were performed in each beagle dog. The anastomosis time, postoperative complications, body weight, blasting pressure of anastomosis and serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, creatinine, blood urea nitrogen, and serum magnesium were compared between the two groups. The healing of anastomosis and degradation of magnesium alloy were observed. The histopathological features of heart, liver, spleen and kidney were examined in the two groups. RESULTS: There were no significant differences in anastomosis time, body weight, postoperative complications, anastomotic bursting pressure between the two groups. The anastomosis was healed well, and no dramatic inflammatory cell infiltration was observed. Magnesium alloy could be degraded completely in the animal body within 90 days. There were no significant differences in serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, creatinine, blood urea nitrogen and serum magnesium between the two groups. Histopathological examination showed that the degradation of magnesium alloy did not harm the important organs (liver, kidney, heart, brain and spleen). CONCLUSIONS: Magnesium alloy stapler is safe and feasible for gastrointestinal anastomosis in beagle dogs. The degradation of magnesium alloy does not harm the healing of anastomosis and other important organs. Magnesium alloy stapler may be a candidate of biodegradable and safe material of stapler for gastrointestinal anastomosis in human.