ABSTRACT
The association of TRIM29 overexpression with cancer progression and poor clinical prognosis has been reported in the context of several types of cancers. In the present study, we investigated the prognostic relevance of TRIM29 and its involvement in the progression of human osteosarcoma. To the best of our knowledge, this is the first study to demonstrate a major role of TRIM29 in osteosarcoma. Our results showed that the expression of TRIM29 in osteosarcoma tissues was much higher than that in normal bone tissues. Furthermore, TRIM29 expression was significantly correlated with tumor size, recurrence, metastasis and overall survival time. High expression of TRIM29 and presence of metastasis were independent predictors of poor prognosis in these patients. Both protein and mRNA expression of TRIM29 in osteosarcoma cell lines were significantly higher than those in osteoblast cell line, hFOB1.19. Moreover, the results indicated that TRIM29 promoted migration and invasive growth of osteosarcoma cells by inducing epithelial-mesenchymal transition. Therefore, ectopic expression of TRIM29 potentially contributes to metastasis and poor prognosis in patients with osteosarcoma. In summary, TRIM29 is a potential prognostic biomarker and a therapeutic target for patients with osteosarcoma.
Subject(s)
Bone Neoplasms/genetics , DNA-Binding Proteins/genetics , Epithelial-Mesenchymal Transition/genetics , Osteosarcoma/genetics , Transcription Factors/genetics , Adolescent , Adult , Biomarkers, Tumor/genetics , Bone Neoplasms/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Child , Disease Progression , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Osteosarcoma/pathology , Prognosis , RNA, Messenger/genetics , Young AdultABSTRACT
Analgesic strategy of a single drug analgesia in bone cancer pain (BCP) has shifted to combined analgesia with different drugs which have different mechanism. After tumor cell inculation, the activation of signal transducer and activator of transcription (STAT3) and extracellular signal-regulated kinase (ERK) signaling pathway are involved in the development and maintenance of BCP, whereas a decrease in the expression of spinal STAT3 and ERK through using their specific blocker, lead to attenuation of BCP. Hence, in this study, we clarified that intrathecal (i.t.) injection of midazolam (MZL) and ropivacaine (Ropi) induces synergistic analgesia on BCP and is accompanied with different mechanisms of these analgesic effect. Hargreaves heat test was used to detect the analgesic effect of single dose of i.t. MZL, Ropi and their combination on the BCP rats. At consecutive daily administration experiment, thermal hyperalgesia was recorded, and immunohistochemical staining was used to detect the expression of c-Fos, spinal glial fibrillary acidic protein (GFAP) and ionized calcium binding adapter molecule-1 (IBA-1). Then, western blot analysis was used to examine spinal TSPO, GFAP, IBA-1, pERK/ERK and pSTAT3/STAT3 levels on day 14 after tumor cell inoculation. i.t. MZL or Ropi showed a short-term analgesia dose-dependently, and MZL displayed better effect on inhibition of pSTAT3 expression than pERK, but Ropi was just the reverse, then consecutive daily administrations of their combination acted synergistically to attenuate thermal hyperalgesia with downregulated spinal 'neuron-astrocytic activation' in the BCP rats. i.t. co-delivery of MZL and Ropi shows synergistic analgesia on the BCP with the inhibition of spinal 'neuron-astrocytic activation'. Spinal different signaling pathway inhibition for MZL and Ropi may be involved in this process.
Subject(s)
Amides/pharmacology , Bone Neoplasms/drug therapy , Cancer Pain/drug therapy , Midazolam/pharmacology , Amides/administration & dosage , Anesthetics, Local/pharmacology , Animals , Bone Neoplasms/pathology , Drug Synergism , Drug Therapy, Combination/methods , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Hypnotics and Sedatives/pharmacology , Injections, Spinal , Midazolam/administration & dosage , Neuroglia/drug effects , Rats, Sprague-Dawley , Receptors, GABA/metabolism , Ropivacaine , STAT3 Transcription Factor/metabolism , Spinal Cord/drug effects , Spinal Cord/metabolismABSTRACT
Despite the knowledge on many genetic variants present in osteosarcoma, the complexity of this disease precludes placing its biology into a simple conceptual framework. RECQL is a DNA helicase involved in DNA mismatch repair and has been reported to be associated with many human cancers. We aimed to investigate the association of RECQL genetic polymorphism with osteosarcoma in a Chinese population. We selected three polymorphisms of the RECQL5 gene (rs820196, rs820200, and rs4789223) in the present study. TaqMan method was utilized for genotyping these three SNPs in 212 patients with osteosarcoma and 240 age- and sex-matched noncancer controls. In our study, we found that CC genotype in rs820196 (17.5 vs 8.3%, P = 0.005) and AA genotype in rs4789223 (21.7 vs 14.2, P < 0.001) were more frequent in osteosarcoma group compared to the control group, respectively. We also found that the C allele of rs820196 (OR = 1.492, 95% CI 1.138 â¼ 1.951; P = 0.004) and A allele of rs4789223 (OR = 1.767, 95% CI: 1.354 â¼ 2.301; P < 0.001) were common in the osteosarcoma patients than those in the control subjects, respectively. Haplotype analysis showed that TTA (OR = 3.469, 95% CI 1.798 â¼ 6.695; P < 0.001) was associated with increased risk for osteosarcoma. However, the TTG (OR = 0.578, 95% CI 0.442 â¼ 0.756) was associated with decreased risk for osteosarcoma. Our results suggested that RECQL5 genetic polymorphisms were associated with osteosarcoma in a Chinese population.
