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血小板内皮细胞黏附分子1(PECAM1)在骨转移的发病机制和治疗中发挥作用。

PECAM1 plays a role in the pathogenesis and treatment of bone metastases.

作者信息

Liang Zhuo-Tao, Li Jia-Ke, Li Jiong, Tang Hao, Guo Chao-Feng, Zhang Hong-Qi

机构信息

Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China.

National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

Front Genet. 2023 Mar 15;14:1151651. doi: 10.3389/fgene.2023.1151651. eCollection 2023.

Abstract

Bone is the third most common metastatic site for all primary tumors, the common primary focus of bone metastases include breast cancer, prostate cancer, and so on. And the median survival time of patients with bone metastases is only 2-3 years. Therefore, it is urgent to develop new targets to diagnose and treat bone metastases. Based on two data sets GSE146661 and GSE77930 associated with bone metastases, it was found that 209 genes differentially expressed in bone metastases group and control group. PECAM1 was selected as hub-gene for the follow-up research after constructing protein-protein interaction (PPI) network and enrichment analysis. Moreover, q-PCR analysis verified that the expression of PECAM1 decreased in bone metastatic tumor tissues. PECAM1 was believed to be possibly related to the function of osteoclasts, we knocked down the expression of PECAM1 with shRNA in lymphocytes extracted from bone marrow nailed blood. The results indicated that sh-PECAM1 treatment could promote osteoclast differentiation, and the sh-PECAM1-treated osteoclast culture medium could significantly promote the proliferation and migration of tumor cells. These results suggested that PECAM1 may be a potential biomarker for the diagnosis and treatment of bone metastases of tumor.

摘要

骨是所有原发性肿瘤第三常见的转移部位,骨转移的常见原发灶包括乳腺癌、前列腺癌等。骨转移患者的中位生存时间仅为2至3年。因此,开发诊断和治疗骨转移的新靶点迫在眉睫。基于两个与骨转移相关的数据集GSE146661和GSE77930,发现骨转移组和对照组中有209个基因差异表达。构建蛋白质-蛋白质相互作用(PPI)网络并进行富集分析后,选择PECAM1作为后续研究的枢纽基因。此外,q-PCR分析证实骨转移瘤组织中PECAM1的表达降低。PECAM1被认为可能与破骨细胞的功能有关,我们用shRNA敲低从骨髓钉血中提取的淋巴细胞中PECAM1的表达。结果表明,sh-PECAM1处理可促进破骨细胞分化,且经sh-PECAM1处理的破骨细胞培养基可显著促进肿瘤细胞的增殖和迁移。这些结果表明,PECAM1可能是肿瘤骨转移诊断和治疗的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee58/10050551/9f830cfeb212/fgene-14-1151651-g001.jpg

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