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促进神经母细胞瘤的细胞增殖和转移,通过调节 PI3K/Akt 信号通路。

Facilitates Cell Proliferation and Metastasis in Neuroblastoma via Regulating the PI3K/Akt Signaling Pathway.

机构信息

Department of Pediatric Hematology/Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.

Department of Medicine, Quzhou College of Technology, Quzhou, Zhejiang Province 324000, China.

出版信息

Curr Cancer Drug Targets. 2022;22(11):919-930. doi: 10.2174/1568009622666220728123748.

DOI:10.2174/1568009622666220728123748
PMID:35909289
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9900700/
Abstract

PURPOSE

The study aims to access the value of B-cell lymphoma/leukemia 11A (BCL11A) in the prognosis of patients with neuroblastoma (NB) and to explore its role and possible mechanism in NB.

METHODS

Tumor specimens from 53 children with neuroblastoma were evaluated for the relationship between BCL11A expression level and prognosis of NB patients. Online datasets like SEQC and Asgharzadeh were analyzed to further check out the suppose.The role of BCL11A in the proliferation and migration of NB cells was studied by functional experiments such as CCK8, colony formation, flow cytometry, transwell and wound healing assay after knocking down BCL11A by small interfering RNA (siRNA) in vitro. The protein makers of the potential pathways were tested by western blot.

RESULTS

High expression of BCL11A in NB patients was closely correlated with high-risk and poor prognosis. The proliferation and migration abilities of NB cell lines SK-N-BE(2) and IMR-32 were significantly impaired by silencing BCL11A. Downregulation of BCL11A expression level in NB cells inhibited the epithelial-mesenchymal transition (EMT) process and affected the PI3K/Akt signaling pathway.

CONCLUSION

As a prognostic indicator of survival in NB patients, BCL11A might serve as a potential therapeutic target. BCL11A played a regulatory role in cell proliferation, invasion, and migration in NB, which may be through the PI3K/AKT signaling pathway and induce EMT.

摘要

目的

本研究旨在评估 B 细胞淋巴瘤/白血病 11A(BCL11A)在神经母细胞瘤(NB)患者预后中的价值,并探讨其在 NB 中的作用及可能的机制。

方法

对 53 例神经母细胞瘤患儿的肿瘤标本进行评估,分析 BCL11A 表达水平与 NB 患者预后的关系。在线数据集如 SEQC 和 Asgharzadeh 进行分析以进一步验证假设。通过体外小干扰 RNA(siRNA)敲低 BCL11A 研究 BCL11A 对 NB 细胞增殖和迁移的作用,采用 CCK8、集落形成、流式细胞术、Transwell 和划痕愈合实验。通过 Western blot 检测潜在通路的蛋白标志物。

结果

NB 患者中 BCL11A 的高表达与高危和预后不良密切相关。沉默 BCL11A 可显著抑制 NB 细胞系 SK-N-BE(2)和 IMR-32 的增殖和迁移能力。NB 细胞中 BCL11A 表达水平的下调抑制了上皮间质转化(EMT)过程,并影响了 PI3K/Akt 信号通路。

结论

BCL11A 作为 NB 患者生存的预后指标,可能成为潜在的治疗靶点。BCL11A 在 NB 中对细胞增殖、侵袭和迁移起调节作用,可能通过 PI3K/AKT 信号通路诱导 EMT。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b11/9900700/8757bd90095b/CCDT-22-919_F6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b11/9900700/b09e02458cd2/CCDT-22-919_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b11/9900700/ff4bd6fc43d0/CCDT-22-919_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b11/9900700/3b59d722288b/CCDT-22-919_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b11/9900700/83ae2df7b67d/CCDT-22-919_F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b11/9900700/5a0733864a7e/CCDT-22-919_F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b11/9900700/8757bd90095b/CCDT-22-919_F6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b11/9900700/b09e02458cd2/CCDT-22-919_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b11/9900700/ff4bd6fc43d0/CCDT-22-919_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b11/9900700/3b59d722288b/CCDT-22-919_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b11/9900700/83ae2df7b67d/CCDT-22-919_F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b11/9900700/5a0733864a7e/CCDT-22-919_F5.jpg
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