Screening and Interaction Analysis of Key Genes in miR-542-3p Over-Expressed Osteosarcoma Cells by Bioinformatics.
- 作者列表："Li Z","Zhang P","Feng F","Zhang Q
BACKGROUND:Osteosarcoma is one of the most serious primary malignant bone tumors that threaten the life of children and adolescents. However, the mechanism underlying and how to prevent or treat the disease have not been well understood. Aims & Objective: This aim of the present study was identify the key genes and explore novel insights into the molecular mechanism of miR-542-3p over-expressed Osteosarcoma. MATERIALS & METHODS:Gene expression profile data GDS5367 was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were screened using GEO2R, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the DIVID database. And protein-protein interaction (PPI) network was constructed by STRING database. In addition, most highly connected module was screened by plugin MCODE and hub genes by plugin CytoHubba. Furthermore, UALCAN and The Cancer Genome Atlas were performed for survival analysis. RESULT:In total, 1421 DEGs were identified, including 598 genes were up-regulated and 823 genes were down-regulated. GO analysis showed that DEGs were classified into three groups and DEGs mainly enriched in Steroid biosynthesis, Ubiquitin mediated proteolysis and p53 signaling pathway. Six hub genes (UBA52, RNF114, UBE2H, TRIP12, HNRNPC and PTBP1) may be key genes with the progression of osteosarcoma. CONCLUSION:The results could better understand the mechanism of osteosarcoma, which may facilitate a novel insight into treatment targets.
背景: 骨肉瘤是严重威胁儿童和青少年生命的原发性骨肿瘤之一。然而，其潜在的机制以及如何预防或治疗该疾病还没有得到很好的理解。目的和目的: 本研究的目的是确定关键基因，并探索 miR-542-3p 过表达骨肉瘤的分子机制。 材料与方法: 从 Gene expression Omnibus (GEO) 数据库下载基因表达谱数据 GDS5367。使用 GEO2R 筛选差异表达基因 (DEGs)，使用 DIVID 数据库进行基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 分析。并通过 STRING 数据库构建蛋白质-蛋白质相互作用 (PPI) 网络。此外，大多数高度连接的模块通过 plugin MCODE 和 hub 基因通过 plugin CytoHubba 进行筛选。此外，进行 UALCAN 和癌症基因组图谱的生存分析。 结果: 共鉴定出 1421 个 DEGs，其中上调基因 598 个，下调基因 823 个。GO 分析显示，DEGs 分为三组，主要富集于类固醇生物合成、泛素介导的蛋白水解和 p53 信号通路。6 个中心基因 (UBA52 、 RNF114 、 UBE2H 、 TRIP12 、 HNRNPC 和 PTBP1) 可能是骨肉瘤进展的关键基因。 结论: 研究结果能更好地理解骨肉瘤的发病机制，为寻找新的治疗靶点提供了可能。
METHODS:BACKGROUND:Osteosarcoma is the most common primary bone malignancy in children and adolescents. In order to find factors related to its recurrence, and thus improve recovery prospects, a powerful clinical signature is needed. Long noncoding RNAs (lncRNAs) are essential in osteosarcoma processes and development, and here we report significant lncRNAs to aid in earlier diagnosis of osteosarcoma. METHODS:A univariate Cox proportional hazards regression analysis and a multivariate Cox regression analysis were used to analyze osteosarcoma patients' lncRNA expression data from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET), a public database. RESULTS:A lncRNA signature consisting of three lncRNAs (RP1-261G23.7, RP11-69E11.4 and SATB2-AS1) was selected. The signature was used to sort patients into high-risk and low-risk groups with meaningful recurrence rates (median recurrence time 16.80 vs. >128.22 months, log-rank test, P143.80 months, log-rank test, P=0.006). A multivariate Cox regression analysis showed that the significant lncRNA was an independent prognostic factor for osteosarcoma patients. Functional analysis suggests that these lncRNAs were related to the PI3K-Akt signaling pathway, the Wnt signaling pathway, and the G-protein coupled receptor signaling pathway, all of which have various, important roles in osteosarcoma development. The significant 3-lncRNA set could be a novel prediction biomarker that could aid in treatment and also predict the likelihood of recurrence of osteosarcoma in patients.
METHODS::Long non-coding RNAs (lncRNAs) regulates the initiation and progression of osteosarcoma (OS), specifically lncRNA RP11-361F15.2 has been shown to play prominent roles in tumorigenesis. Previously, M2-Like polarization of tumor-associated macrophages (TAMs) has been identified to play a key role in cancer migration/invasion. Hence, it is essential to understand the role of RP11-361F15.2 in tumorigenesis and its association with M2-Like polarization of TAMs. The results indicate that RP11-361F15.2 is significantly increased in OS tissues, and its expression is positively correlated with cytoplasmic polyadenylation element binding protein 4 (CPEB4) expression and negatively associated with miR-30c-5p expression. Further, overexpression of RP11-361F15.2 increased OS cell migration/invasion and M2-Like polarization of TAMs in vitro, as well as promoted xenograft tumor growth in vivo. Mechanistically, luciferase reporter assays indicated that RP11-361F15.2 upregulated CPEB4 expression by competitively binding to miR-30c-5p. Further, we have identified that RP11-361F15.2 promotes CPEB4-mediated tumorigenesis and M2-Like polarization of TAMs through miR-30c-5p in OS. We also identified that RP11-361F15.2 acts as competitive endogenous RNA (ceRNA) against miR-30c-5p thereby binding and activating CPEB4. This RP11-361F15.2/miR-30c-5p/CPEB4 loop could be used as a potential therapeutic strategy for the treatment of OS.
METHODS:PURPOSE:The objective of this study was to investigate potential correlations between pathologic fractures (PFs) and prognosis of patients with primary central high-grade osteosarcoma of the extremities. METHODS:We retrospectively analyzed 2,847 patients registered in the Consecutive Cooperative Osteosarcoma Study Group database with primary central high-grade osteosarcoma of the extremities, treated between 1980 and 2010. Intended treatment included pre- and postoperative chemotherapy and surgery. Univariable and multivariable survival analyses were performed for all patients and then differentiated for adult and pediatric (≤ 18 years at time of diagnosis) patients. RESULTS:A total of 2,193 patients were ≤ 18 years of age; 11.3% of all patients had PFs. In the overall cohort, presence of PF correlated significantly with tumor site, histologic subtype, relative tumor size, and primary metastases, but not with body mass index or local surgical remission. In univariable analysis, 5-year overall survival (OAS) of patients with and without PF was 63% versus 71%, respectively (P = .007), and 5-year event-free survival (EFS) was 51% versus 58% (P = .026). In pediatric patients, OAS and EFS did not differ significantly between patients with and without PF. In adults, 5-year OAS in patients with and without PF was 46% versus 69% (P < .001), and 5-year EFS was 36% versus 56% (P < .001). In multivariable analysis, PF was not a statistically significant factor for OAS or EFS in the total cohort or in pediatric patients. In adult patients, PF remained an independent prognostic factor for OAS (P = .013; hazard ratio [HR], 1.893). It was not a significant prognostic factor for EFS (P = .263; HR, 1.312). CONCLUSION:In this largest study to date with extremity osteosarcomas, we observed the occurrence of PF to correlate with inferior OAS expectancies in adult but not in pediatric patients.