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敲低骨肉瘤细胞中的 Siglec-15 可通过靶向 Siglec-15/STAT3/Bcl-2 通路抑制增殖,同时促进细胞凋亡和细胞焦亡。

Knocking down Siglec-15 in osteosarcoma cells inhibits proliferation while promoting apoptosis and pyroptosis by targeting the Siglec-15/STAT3/Bcl-2 pathway.

机构信息

Department of Orthopedic Oncology, the Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China; Qingdao Medical College of Qingdao University, Qingdao, People's Republic of China.

Qingdao Medical College of Qingdao University, Qingdao, People's Republic of China; Department of Spinal Surgery, the Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.

出版信息

Adv Med Sci. 2022 Sep;67(2):187-195. doi: 10.1016/j.advms.2022.03.001. Epub 2022 Apr 7.

DOI:10.1016/j.advms.2022.03.001
PMID:35398779
Abstract

PURPOSE

Sialic acid-bound immunoglobulin lectin 15 (Siglec-15) plays a crucial role in many kinds of tumors. The relationship between Siglec-15 and the prognosis of osteosarcoma patients and its role in the apoptosis and pyroptosis of osteosarcoma cells are not sufficiently understood. Our study aimed to investigate the function of Siglec-15 in osteosarcoma cells and its effect on tumor cell proliferation, apoptosis and pyroptosis.

MATERIALS AND METHODS

The Siglec-15 expression in pathological sections of osteosarcoma patients was analyzed and the overall survival time related to the expression of Siglec-15 was further analyzed. Next, we detected the expression of Siglec-15 in osteosarcoma cells and downregulated the expression of Siglec-15 by small interfering RNA (siRNA). The proliferation, apoptosis and pyroptosis of osteosarcoma cells were studied by proliferation and apoptosis kits and Western blotting. Furthermore, the Siglec-15 signaling pathway was examined, which may be involved in the observed cellular effects.

RESULTS

We demonstrated the expression of Siglec-15 in osteosarcoma cells. SiRNA-mediated downregulation of Siglec-15 was successful. We found that knockdown of Siglec-15 in osteosarcoma cell lines significantly inhibited proliferation while promoting apoptosis. Further investigation showed that the expression of proliferation-related proteins was downregulated and that apoptosis- and pyroptosis-related proteins were upregulated. In addition, we found that Siglec-15 may inhibit proliferation while inducing apoptosis and pyroptosis via the (Signal Transducer and Activator of Transcription 3) STAT3/Bcl-2 pathway in osteosarcoma.

CONCLUSIONS

In this study, we demonstrated that the ablation of Siglec-15 in osteosarcoma inhibited proliferation and promoted apoptosis and pyroptosis by targeting the Siglec-15/STAT3/Bcl-2 pathway.

摘要

目的

唾液酸结合免疫球蛋白样凝集素 15(Siglec-15)在多种肿瘤中发挥着关键作用。Siglec-15 与骨肉瘤患者的预后之间的关系及其在骨肉瘤细胞凋亡和细胞焦亡中的作用尚不完全清楚。本研究旨在探讨 Siglec-15 在骨肉瘤细胞中的功能及其对肿瘤细胞增殖、凋亡和细胞焦亡的影响。

材料与方法

分析骨肉瘤患者病理切片中 Siglec-15 的表达情况,并进一步分析 Siglec-15 表达与总生存时间的关系。然后,我们检测了骨肉瘤细胞中 Siglec-15 的表达,并通过小干扰 RNA(siRNA)下调 Siglec-15 的表达。通过增殖和凋亡试剂盒以及 Western blot 检测骨肉瘤细胞的增殖、凋亡和细胞焦亡。此外,还研究了可能参与观察到的细胞效应的 Siglec-15 信号通路。

结果

我们证实了 Siglec-15 在骨肉瘤细胞中的表达。siRNA 介导的 Siglec-15 下调是成功的。我们发现,骨肉瘤细胞系中 Siglec-15 的敲低显著抑制增殖,同时促进凋亡。进一步研究表明,增殖相关蛋白的表达下调,凋亡和细胞焦亡相关蛋白的表达上调。此外,我们发现 Siglec-15 可能通过 STAT3/Bcl-2 通路抑制骨肉瘤中的增殖,同时诱导凋亡和细胞焦亡。

结论

在这项研究中,我们证明了通过靶向 Siglec-15/STAT3/Bcl-2 通路,骨肉瘤中 Siglec-15 的缺失抑制了增殖,促进了凋亡和细胞焦亡。

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