Expression and clinical significance of zinc-α2-glycoprotein 1 in osteosarcoma tissues / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the expression of zinc-α2-glycoprotein 1 (AZGP1) in osteosarcoma tissue and its relationship with clinicopathological features and prognosis of patients. Methods: A total of 62 pairs of cancer tissue and adjacent normal tissue samples from patients with osteosarcoma treated in the Department of Orthopedics, Second People's Hospital of Nanyang City were collected from August 2012 to August 2014. The expressions of AZGP1 in osteosarcoma tissues and adjacent tissues were detected by using immunohistochemical staining. All patients were followed up on the second day after the operation. The deadline was August 31, 2019. All patients were followed up for 5 years, with death as the end event. The number of end events within 5 years and overall survival (OS) time of the patients were recorded. Kaplan-Meier method was used for survival analysis, and Cox proportional hazard model was used for multivariate analysis of factors affecting patients’ survival. Results: The positive expression rate of AZGP1 in the osteosarcoma tissues was significantly higher than that in the adjacent tissues (77.42% vs 32.26%, P<0.01). There were significant differences in the positive expression rates of AZGP1 in patients with different Eneeking stages, soft tissue infiltration or not and lung metastasis conditions (all P<0.05). Kaplan-Meier survival analysis showed that the average OS time and 5-year OS rate of patients in the AZGP1 positive expression group were significantly lower than those in the negative expression group [(24.19±2.68) months vs (43.07±3.70) months, P<0.01; 18.75% vs 64.29%, P<0.01]. The lung metastasis and positive expression of AZGP1 were risk factors affecting the prognosis of patients with osteosarcoma (HR=3.407, 3.647, all P<0.05). Conclusion: AZGP1 is highly expressed in osteosarcoma tissues, and it is related to the malignant indicators and prognosis of patients. It may be a potential marker for evaluating the prognosis of osteosarcoma patients.

LncRNA Linc00511 promotes osteosarcoma cell proliferation and migration through sponging miR-765.

Long noncoding RNA (lncRNA) Linc00511 is a novel lncRNA, and it was reported to play important roles in the progression and carcinogenesis of several tumors. However, the expression and biological roles of Linc00511 in osteosarcoma were still unknown. In this research, we showed that the expression of Linc00511 was upregulated in osteosarcoma samples and cell lines. Ectopic expression of Linc00511 promoted osteosarcoma cell growth, colony formation, and migration. Moreover, overexpression of Linc00511 enhanced the epithelial-mesenchymal transition progression in osteosarcoma cell. In addition, we showed that elevated expression of Linc00511 suppressed microRNA-765 (miR-765) expression and promoted apurinic/apyrimidinic endonuclease 1 (APE1) expression in osteosarcoma cell. The expression of miR-765 was downregulated in osteosarcoma cells and samples and was negatively related to Linc00511 expression in osteosarcoma tissues. Ectopic expression of miR-765 inhibited osteosarcoma cell growth and migration. Furthermore, we showed that Linc00511 overexpression promoted MG-63 cells proliferation, colony formation, and migration via downregulation of miR-765. These results suggested that Linc00511 played as an oncogene in the development of osteosarcoma.

Gigantol inhibits the proliferation, migration and invasion of osteosarcoma cells by NF-κB/PRL-3 pathway / 中国肿瘤生物治疗杂志

@#To study the inhibitory effect of gigantol on proliferation, migration and invasion of human osteosarcoma U20S cells and to explore the mechanism. Methods: After being treated with different concentrations (10, 25, 50, 75, 100, 150 µmol/L) of gigantol for 24 and 48 h, the proliferation of U20S cells was detected by CCK-8 assay. Transwell assay was used to detect the effects of 25 µmol/L and 50 µmol/L gigantol on the migration and invasion abilities of U20S cells. The lipopolysaccharide (LPS) was used to induce inflammatory reaction in U20S cells before gigantol treatment; qPCR and WB were used to detect the mRNA and protein expressions of NF-κB (p65), TNF-α, IL-6 and PRL-3, respectively. Results: Different concentrations of gigantol could all inhibit the proliferation of sarcoma U20S cells at different time (P<0.05 or P<0.01). The 25 µmol/L and 50 µmol/L of gigantol could significantly inhibit the migration and invasion of osteosarcoma U20S cells (all P<0.01); at the same time, it could inhibit the protein expressions of NF-κB, TNF-α, IL-6 and PRL-3 (P<0.05 or P<0.01). After LPS induction, the mRNA and protein expressions of NF-κB, TNF-α, IL-6 and PRL-3 in U20S cells were significantly increased (all P<0.01); however, the consequent treatment with gigantol (25 and 50 µmol/L) reversed the effects of LPS on U20S cells obviously (P<0.05 or P<0.01). Conclusion: Gigantol can inhibit the proliferation, migration and invasion of osteosarcoma U20S cells, and its mechanism may be related to the regulation of NF-κB/PRL-3 signaling pathway.

MicroRNA-448 suppresses osteosarcoma cell proliferation and invasion through targeting EPHA7.

Osteosarcoma is the most common type of malignant bone tumor, often affecting adolescents and children. MicroRNAs (miRNAs) are a group of small, non-protein coding, endogenous RNAs that play critical roles in osteosarcoma tumorigenesis. In our study, we demonstrated that miR-448 expression was downregulated in osteosarcoma tissues and cell lines. Overexpression of miR-448 suppressed osteosarcoma cell proliferation, colony formation and migration. Moreover, we found that EPHA7 was a direct target gene of miR-448 in osteosarcoma cells. We further demonstrated that the EPHA7 expression level was upregulated in osteosarcoma tissues. Interestingly, the expression level of EPHA7 was inversely correlated with the expression level of miR-448 in osteosarcoma tissues. In addition, elevated expression of miR-448 suppressed osteosarcoma cell proliferation and invasion through targeting EPHA7. Taken together, these findings suggest that miR-448 functioned as a tumor suppressor gene in the development of osteosarcoma through targeting EPHA7.

Assessment of the relationship between ACE I/D gene polymorphism and renal allograft survival.

BACKGROUND AND OBJECTIVE: The relationship between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and renal allograft survival after renal transplantation from the published reports are still debatable. This study was performed to evaluate the relationship between the ACE I/D gene polymorphism and renal allograft survival after renal transplantation using meta-analysis. METHOD: Eligible studies were identified from PubMed and Cochrane Library on 1 November 2014, and eligible studies were recruited and synthesized using a meta-analysis methodology. RESULTS: Twelve investigations were included in this meta-analysis for the assessment of the relationship between the ACE I/D gene polymorphism and renal allograft survival. In this meta-analysis, the ACE I/D gene polymorphism was not associated with renal allograft survival after renal transplantation for overall populations, Caucasians, Brazilians and Africans. Interestingly, the ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. CONCLUSIONS: ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. However, more studies should be performed to confirm this association.