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ESCRT转录组相关特征的综合分析及LMO7-AS1在骨肉瘤中的调控作用鉴定。

Comprehensive analysis of ESCRT transcriptome-associated signatures and identification of the regulatory role of LMO7-AS1 in osteosarcoma.

作者信息

Zhao Shibing, Tian Dasheng, Huang Fei, Wang Lei, Cheng Jinhao, He Zhitao, Shen Qitian, Liang Shuai, Gong Deliang, Liu Jun, Yi Chengfeng, Zhang Chun, Bian Erbao, Jing Juehua, Wang Tao

机构信息

Department of Orthopaedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.

Institute of Orthopaedics, Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.

出版信息

Cancer Cell Int. 2025 Jan 30;25(1):29. doi: 10.1186/s12935-025-03659-4.

Abstract

Osteosarcoma (OS) is a commonly observed malignant tumor in orthopedics that has a very poor prognosis. The endosomal sorting complex required for transport (ESCRT) is important for the development and progression of cancer and may be a significant target for cancer therapy. First, we built a prognostic signature using 7 ESCRT-related genes (ERGs) to predict OS patient prognosis. Analysis of internal and external datasets revealed that the ERG signature has good predictive ability and reproducibility. Immune analysis demonstrated a significant correlation between OS patient immune status and ERG signature score. Moreover, ERG signature score was found to be associated with the response of OS patients to immunotherapy and anticancer drugs. Additionally, we constructed a prognostic signature consisting of 10 ESCRT-related long noncoding RNAs (ERLs) that effectively predicted the prognosis of OS patients. Furthermore, two subgroups of OS patients with distinct prognoses (clusters 1 and 2) were identified. Finally, LMO7-AS1 was chosen for functional experimental validation. The knockdown of LMO7-AS1 suppressed the malignant progression of OS cells. Furthermore, transcriptome sequencing was performed on OS cells and revealed a correlation between LMO7-AS1 and the PI3K-Akt signaling pathway. In conclusion, our ESCRT transcriptome-associated signatures can act as prognostic biomarkers for OS, and LMO7-AS1 is a novel therapeutic target for the treatment of OS.

摘要

骨肉瘤(OS)是骨科中常见的恶性肿瘤,预后很差。转运所需的内体分选复合体(ESCRT)对癌症的发生和发展很重要,可能是癌症治疗的重要靶点。首先,我们使用7个ESCRT相关基因(ERG)构建了一个预后特征来预测骨肉瘤患者的预后。对内部和外部数据集的分析表明,ERG特征具有良好的预测能力和可重复性。免疫分析显示骨肉瘤患者免疫状态与ERG特征评分之间存在显著相关性。此外,发现ERG特征评分与骨肉瘤患者对免疫治疗和抗癌药物的反应有关。此外,我们构建了一个由10个ESCRT相关长链非编码RNA(ERL)组成的预后特征,该特征有效地预测了骨肉瘤患者的预后。此外,还确定了预后不同的两个骨肉瘤患者亚组(簇1和簇2)。最后,选择LMO7-AS1进行功能实验验证。LMO7-AS1的敲低抑制了骨肉瘤细胞的恶性进展。此外,对骨肉瘤细胞进行了转录组测序,揭示了LMO7-AS1与PI3K-Akt信号通路之间的相关性。总之,我们的ESCRT转录组相关特征可作为骨肉瘤的预后生物标志物,LMO7-AS1是治疗骨肉瘤的新治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a39/11783933/aaee137365bc/12935_2025_3659_Fig1_HTML.jpg

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