MicroRNA-129-5p alleviates spinal cord injury in mice via suppressing the apoptosis and inflammatory response through HMGB1/TLR4/NF-κB pathway.

Secondary injury after spinal cord injury (SCI) is one reversible pathological change mainly involving excessive inflammatory response and neuro-apoptosis. Since in recent years, microRNAs (miRNAs) have been proposed as novel regulators of inflammation in different disease conditions. However, the role of miRNAs in the inflammatory response and apoptosis of secondary injury after SCI remains to be fully elucidated. Here, we tried to explore the influence and mechanism of miRNAs on the neuron inflammatory response and apoptosis after SCI. The expression profiles of miRNA were examined using miRNA microarray, and among the candidate miRNAs, miR-129-5p was found to be the most down-regulated miRNA in spinal tissues. Overexpression of miR-129-5p using agomir-miR-129-5p promoted injury mice functional recovery, suppressed the apoptosis and alleviated inflammatory response in spinal tissues. Using LPS-induced BV-2 cell model, we found miR-129-5p was also proved in protecting inflammatory response and cell apoptosis in vitro. High-mobility group protein B1 (HMGB1), a well-known inflammatory mediator, was found to be directly targeted by miR-129-5p and it was associated with the inhibitory effect of miR-129-5p on the activation of toll-like receptor (TLR)-4 (TLR4)/ nuclear factor-κB (NF-κB) pathway in vitro and in vivo. Further experiments revealed that the anti-apoptosis and anti-inflammatory effects of miR-129-5p were reversed by HMGB1 overexpression in BV-2 cells. Collectively, these data revealed that miR-129-5p alleviated SCI in mice via suppressing the apoptosis and inflammatory response through HMGB1//TLR4/NF-κB pathway. Our data suggest that up-regulation of miR-129-5p may be a novel therapeutic target for SCI.

Down-regulation of microRNA-203a suppresses IL-1ß-induced inflammation and cartilage degradation in human chondrocytes through Smad3 signaling.

Osteoarthritis (OA) is a chronic and prevalent degenerative musculoskeletal disorder, which is characterized by articular cartilage degradation and joint inflammation. MicroRNA-203a (miR-203a) has been shown to be involved in multiple pathological processes during OA, but little is known about its function in chondrocyte extracellular matrix (ECM) degradation. In the present study, we aimed to elucidate the effects of miR-203a on articular cartilage degradation and joint inflammation. We observed that the miR-203a level was significantly up-regulated in OA tissues and in an in vitro model of OA, respectively. Inhibition of miR-203a significantly alleviated the interleukin (IL)-1ß-induced inflammatory response and ECM degradation in chondrocytes. Moreover, mothers against decapentaplegic homolog 3 (Smad3), a key factor in maintaining chondrocyte homeostasis, was identified as a putative target of miR-203a in chondrocytes. More importantly, inhibition of Smad3 impaired the inhibitory effects of the miR-203a on IL-1ß-induced inflammatory response and ECM degradation. Collectively, these results demonstrated that miR-203a may contribute to articular cartilage degradation of OA by targeting Smad3, suggesting a novel therapeutic target for the treatment of OA.

CBX3 predicts an unfavorable prognosis and promotes tumorigenesis in osteosarcoma.

CBX3, namely chromobox protein homolog 3, a member of the heterochomatin protein 1 (HP1) family, has been shown to be associated with the tumorigenesis of various types of cancer. The aim of the present study was to assess the biological role and the clinicopathological importance of CBX3 in osteosarcoma. The Oncomine database was utilized to determine the CBX3 expression in sarcoma patients. A retrospective cohort study was conducted to evaluate the prognostic value of CBX3 expression. In addition, correlations between the clinicopathological features of the osteosarcoma patients and CBX3 expression were assessed and involved recurrence, distant metastasis, lymph node metastasis, response to chemotherapy, pathological differentiation, clinical stage, anatomic location, tumor size and age. To investigate the function of CBX3 in osteosarcoma, a small interfering RNA for CBX3 was designed and this was used for the transfection of osteosarcoma MG63 cells. Then, the effects of CBX3 on proliferation, cell cycle distribution and apoptosis of osteosarcoma cells were investigated via CCK­8 assay and cell cycle assay and cell apoptosis analysis, respectively. Based on our findings, upregulation of CBX3 expression was noted both in osteosarcoma and also other sarcoma types, which included pleomorphic liposarcoma, myxofibrosarcoma, myxoid/round cell liposarcoma and dedifferentiated liposarcoma. In addition, based on the retrospective cohort study, CBX3 expression was associated with the disease­free survival (DFS) and overall survival (OS) of the osteosarcoma patients and a large tumor size, high distant metastasis rate and high clinical stage rate. In addition, the proliferation ability was blocked by the knockdown of CBX3 through the application of CBX3 siRNA, and CBX3 knockdown also led to increased apoptosis and cell cycle arrest at G0 and G1 phases in osteosarcoma cells. CBX3 is highly expressed in human osteosarcoma tissues. Meanwhile, high CBX3 is a predictor of the poor prognosis of osteosarcoma patients. To conclude, the growth of osteosarcoma can be promoted by CBX3, which may be used as an independent potential prognostic biomarker for patients suffering from osteosarcoma.

hsa_circ_0081143 promotes cisplatin resistance in gastric cancer by targeting miR-646/CDK6 pathway.

BACKGROUND: Increasing studies indicated that circRNAs play critical roles in tumor progression. However, the roles and underlying mechanisms of circRNAs in gastric cancer (GC) remain largely unclear. METHODS: Microarray assay was used to screen the abnormally expressed circRNAs in GC. Cell viability assay, transwell assay and in vivo assay were performed to assess the effects of hsa_circ_0081143 on GC cells. Next, interaction between hsa_circ_0081143 and miR-646 was detected by luciferase reporter assay and RNA pull-down assay. RESULTS: High throughput microarray assay showed that hsa_circ_0081143 was upregulated in GC tissues, which was further confirmed by qRT-PCR. Correlation analysis showed that high hsa_circ_0081143 expression was associated with the advanced TNM stage, lymphnode metastases, and poor overall survival of GC patients. Hsa_circ_0081143 inhibition decreased GC cells viability, invasion ability and induced the sensitivity of GC cells to cisplatin (DDP) in vitro. Mechanistically, we showed that hsa_circ_0081143 could act as an endogenous sponge by directly binding to miR-646 and downregulation of miR-646 efficiently reversed the inhibition of CDK6 induced by hsa_circ_008114 knockdown. Additionally, hsa_circ_0081143 silencing suppressed the tumorigenesis and remarkably enhance DDP inhibitory effects of GC cells in vivo. CONCLUSIONS: Our study indicated a novel regulatory loop that hsa_circ_0081143/miR-646/CDK6 axis in GC progression. These data suggested that hsa_circ_0081143 might act as a potential novel therapeutic strategy for GC treatment.

Report: Bacterial susceptibility and resistance analysis of traumatic osteomyelitis.

With the rapid development of industry, agriculture and transportation, the high energy trauma happened accordingly, thus greatly increased the incidence of traumatic osteomyelitis. The clinical traumatic osteomyelitis was mainly the local bone tissue inflammation caused by bacteria infection as trauma or iatrogenic causes. The delaying recovery could cause bone defection or bone nonunion. The purpose of this paper was to contribute new reference for the clinical prevention and treatment through tremendous of disease-causing bacteria susceptibility and resistance analysis of osteomyelitis.

The association of XPG and MMS19L polymorphisms response to chemotherapy in osteosarcoma.

OBJECTIVE: To assess the role of XPG, XPC, CCNH and MMS19L polymorphisms response to chemotherapy in osteosarcoma, and the clinical outcome of osteosarcoma. METHODS: One hundred and sixty eight osteosarcoma patients who were histologically confirmed were enrolled in our study between January 2007 and March 2009. Genotyping of XPG, XPC, CCNH and MMS19L was performed in a 384-well plate format on the MassARRAY® platform. RESULTS: Individuals with rs2296147 TT genotype showed a better response as compared with CC genotype, with the OR (95% CI) of 3.89(1.49-10.95). Those carrying rs29001322 TT genotype presented better response to chemotherapy, and the OR (95% CI) was as high as 12.25(2.63-121.84). Patients carrying TT genotype of XPG rs2296147 and MMS19L rs29001322 showed a significantly longer overall survival than CC genotype, they had 0.37 and 0.31-fold risk of death when compared with wide-type of this gene. CONCLUSIONS: XPG rs2296147 and MMS19L rs29001322 are correlated with response to chemotherapy and prognosis of osteosarcoma. Our findings would provide important evidence for prognostic and therapeutic implications in osteosarcoma.