RESUMO
BACKGROUND: Accumulating evidence has suggested the crucial roles of differentially expressed miRNAs in osteosarcoma progression. MiR-139-5p was decreased in various cancers. However, the role of miR-139-5p in the development of osteosarcoma and the underlying mechanism remain to be addressed. METHODS: MiR-139-5p and DNA methyltransferase-1 (DNMT1) mRNA expressions in osteosarcoma tissues and cells were detected by qRT-PCR and western blot analysis. The effects of miR-139-5p and DNMT1 on osteosarcoma cell migration, invasion and epithelial-mesenchymal transition (EMT) were investigated through cell migration and invasion assays, and western blot analysis. The relationship between miR-139-5p and DNMT1was explored using luciferase reporter analysis and western blot. A xenograft tumor model was employed to verify the effects of miR-139-5p on osteosarcoma. RESULTS: We found that miR-139-5p was strikingly decreased in osteosarcoma tissues and cell lines. MiR-139-5p over-expression suppressed osteosarcoma cell growth, migration and invasion, while loss of miR-139-5p promoted osteosarcoma cell proliferation, migration and invasion. Following, we characterized that DNMT1 was a direct target of miR-139-5p that interacted with the 3'-untranslated region of DNMT1. MiR-139-5p regulated a down-regulation in DNMT1 protein expression levels. We also found that DNMT1 expression was increased and negatively correlated with miR-139-5p expression in osteosarcoma tissues clinically. Xenograft tumor analysis suggested that miR-139-5p over-expression reduced tumor growth in osteosarcoma in vivo through decreasing DNMT1 expressions. CONCLUSION: MiR-139-5p suppressed the osteosarcoma progression by reducing DNMT1, supplying new insight into the molecular mechanism uncovering osteosarcoma growth.
Assuntos
Neoplasias Ósseas/genética , DNA (Citosina-5-)-Metiltransferase 1/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Invasividade Neoplásica/genética , Osteossarcoma/genética , Animais , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Transição Epitelial-Mesenquimal , Humanos , Camundongos Nus , Invasividade Neoplásica/patologia , Osteossarcoma/patologiaRESUMO
OBJECTIVE: To investigate the bacteriology and drug sensitivity of upper urinary tract calculi patients, and to provide information for choosing suitable antibiotics. METHODS: In the study, 21 patients who suffered from lithiasis in upper urinary tract and required an emergency drainage for acute obstruction and infection were the "acute group"; 64 patients with calculi in upper urinary tract and accompanied with no infectious symptoms were the "common group". The bacteriology and drug sensitivity of the two groups were investigated. RESULTS: Gram-negative bacteria infected the most common of upper urinary tract calculi patients with infection, accounting for 71.4% in the acute group and 65.7% in the common group, among which Escherichia coli were the predominant ones (35.7% in the acute group and 32.9% in the common group). No difference was found between these two groups in bacterial distribution (P>0.05). Although the average drug resistance rate of Gram-negative bacteria in the acute group was higher than that in the common group, it revealed no significant difference (P>0.05). The drug resistance rate to semisynthetic penicillin, cefuroxime and ceftriaxone were more than 50%, 60%, and 50%, respectively. Quinolones, such as ciprofloxacin and levofloxacin, got a 45% drug resistance. Aminoglycoside, carbapenema were sensitive to Gram-negative bacteria. Cefoperazone/sulbactam and piperacillin/tazobactam were more effective than ceftriaxone and piperacillin, respectively. CONCLUSION: There was no significant difference between upper urinary tract calculi patients with acute infection and common infection in bacteriology and drug sensitivity. Semisynthetic penicillin, the second generation of cephalosporin and quinolone were no longer the good choices of empirical use. Antibiotics combined with ß-lactamase inhibitors would be an ideal empirical therapeutic choice.