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Identification of the Novel Target Genes for Osteosarcoma Therapy Based on Comprehensive Bioinformatic Analysis.
DNA and Cell Biology ( IF 2.6 ) Pub Date : 2020-07-02 , DOI: 10.1089/dna.2020.5377
Xi Zhou 1 , Yu Fan 1 , Weiliang Ye 2 , Binghan Jia 2 , Yuemei Yang 2 , Yong Liu 1
Affiliation  

Osteosarcoma is one of the most common primary malignant tumors of the bone and tends to develop in teenage years. Although multitreatments for the diagnosis and therapy of osteosarcoma have been developed, there are still needs of new methods to prevent and treat the osteosarcoma. Here, we performed bioinformatic analysis to screen for the key genes, molecules, and pathways involved in osteosarcoma survival. Four microarray data sets (GSE99671, GSE87624, GSE65071, and GSE28423), which include data from human bone and osteosarcoma samples, were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed mRNAs and miRNAs were identified. Kyoto Encyclopedia of Genes and Genomes enriched pathways, miRNA-mRNA target, gene/disease relationship, and overall survival was elucidated using related websites and software according to bioinformatic analysis protocols. We found three critical genes miR-29c, blood vessel epicardial substance (BVES), and proteasome 20S subunit beta 2 (PSMB2) through the GEO database and predicting miRNA-mRNA target. Among these genes, BVES and PSMB2 presented a high expression level in osteosarcoma based on GSE99671 and GSE87624 data sets, while miR-29c showed a low expression level in osteosarcoma based on GSE65071 and GSE28423 data sets. Furthermore, we found that the high expression level of miR-29c and BVES associated with better prognosis, while highly expressed PSMB2 associated with poor prognosis. The abnormally expressed mRNAs and miRNAs, which were identified by integrated bioinformatic analysis, provided insights into the molecular mechanisms of osteosarcoma. Notably, we found three critical genes that could be used as novel therapeutic targets for preventing or diagnosing osteosarcoma. Finally, PSMB2 may be the target of miR-29c.

中文翻译:

基于全面的生物信息学分析鉴定骨肉瘤治疗的新靶基因。

骨肉瘤是骨骼最常见的原发性恶性肿瘤之一,并在青少年时期趋于发展。尽管已经开发了用于骨肉瘤的诊断和治疗的多种疗法,但是仍然需要预防和治疗骨肉瘤的新方法。在这里,我们进行了生物信息学分析,以筛选涉及骨肉瘤生存的关键基因,分子和途径。从Gene Expression Omnibus(GEO)数据库下载了四个微阵列数据集(GSE99671,GSE87624,GSE65071和GSE28423),其中包括来自人骨和骨肉瘤样品的数据。鉴定出差异表达的mRNA和miRNA。《京都市基因与基因组百科全书》丰富的途径,miRNA-mRNA靶标,基因/疾病关系,根据生物信息学分析方案,使用相关的网站和软件阐明了总生存期。我们通过GEO数据库发现了三个关键基因miR-29c,心外膜血管物质(BVES)和蛋白酶体20S亚基beta 2(PSMB2),并预测了miRNA-mRNA靶标。在这些基因中,基于GSE99671和GSE87624数据集,BVES和PSMB2在骨肉瘤中呈高表达水平,而基于GSE65071和GSE28423数据集,miR-29c在骨肉瘤中呈低表达水平。此外,我们发现miR-29c和BVES的高表达水平与更好的预后相关,而高表达的PSMB2与不良的预后相关。通过整合的生物信息学分析鉴定出异常表达的mRNA和miRNA,提供了有关骨肉瘤分子机制的见解。值得注意的是,我们发现了三个关键基因,可以用作预防或诊断骨肉瘤的新型治疗靶标。最后,PSMB2可能是miR-29c的靶标。
更新日期:2020-07-10
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