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基于生物信息学分析和实验验证鉴定骨肉瘤细胞系中与致瘤性相关的基因

Identification of tumorigenicity-associated genes in osteosarcoma cell lines based on bioinformatic analysis and experimental validation.

作者信息

Jiang Shaojie, Zhou Fei, Zhang Yanhua, Zhou Weiping, Zhu Linghua, Zhang Miaofeng, Luo Jingfeng, Ma Rui, Xu Xiufang, Zhu Jiying, Dong Xue, Zhang Shuangling, Fang Jie, Sun Jihong, Yang Xiaoming

机构信息

Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310016, China.

School of Medical Imaging, Hangzhou Medical College, Hangzhou, Zhejiang, 310013, China.

出版信息

J Cancer. 2020 Mar 26;11(12):3623-3633. doi: 10.7150/jca.37393. eCollection 2020.

Abstract

Osteosarcoma is the most common primary malignant tumor of bone. Tumorigenic investigation of osteosarcoma cell lines may facilitate preclinical studies of targeted therapy. Therefore, the aim of this study was to explore the tumorigenicity-associated genes in osteosarcoma cells. We found that 138 genes were highly expressed and 86 genes were lowly expressed in highly tumorigenic osteosarcoma cell lines (143B, MNNG/HOS, and SJSA-1) compared with poorly tumorigenic osteosarcoma cell lines (MG-63, Saos-2, and U-2 OS). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that highly expressed genes were associated with amino acids and energy metabolism, while lowly expressed genes were associated with cell cycle and DNA replication. Gene Ontology (GO) analysis showed that highly expressed genes were associated with endoplasmic reticulum stress response and aggrephagy, whereas lowly expressed genes were correlated with extracellular matrix assembly and DNA damage response. Further analysis identified six highly expressed genes and six lowly expressed genes. Three of highly expressed genes (, , and ) were correlated with poor prognosis, while three of lowly expressed genes (, , and ) showed the opposite trend in patients with osteosarcoma. Knockdown of significantly inhibited the tumorigenicity of 143B cells in BALB/c nude mice.

摘要

骨肉瘤是最常见的原发性骨恶性肿瘤。对骨肉瘤细胞系进行致瘤性研究可能有助于靶向治疗的临床前研究。因此,本研究的目的是探索骨肉瘤细胞中与致瘤性相关的基因。我们发现,与低致瘤性骨肉瘤细胞系(MG-63、Saos-2和U-2 OS)相比,高致瘤性骨肉瘤细胞系(143B、MNNG/HOS和SJSA-1)中有138个基因高表达,86个基因低表达。京都基因与基因组百科全书(KEGG)分析显示,高表达基因与氨基酸和能量代谢相关,而低表达基因与细胞周期和DNA复制相关。基因本体论(GO)分析表明,高表达基因与内质网应激反应和聚集体自噬相关,而低表达基因与细胞外基质组装和DNA损伤反应相关。进一步分析确定了6个高表达基因和6个低表达基因。3个高表达基因(、和)与预后不良相关,而3个低表达基因(、和)在骨肉瘤患者中表现出相反的趋势。敲低显著抑制了143B细胞在BALB/c裸鼠中的致瘤性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eabb/7150450/5e0f2a7b945a/jcav11p3623g001.jpg

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