miRNA326-5p Targets DKC1 Gene to Regulate Apoptosis-Related Proteins and Intervene in the Development of Neuroblastoma.

IF 2.6 4区 医学 Q3 CELL BIOLOGY
Analytical Cellular Pathology Pub Date : 2023-07-01 eCollection Date: 2023-01-01 DOI:10.1155/2023/6761894
Xiao-Hui Wang, Shu-Feng Zhang, Hai-Ying Wu, Jian Gao, Lin Wang, Xu-Hui Wang, Tian-Hui Gao
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引用次数: 0

Abstract

Objective: To study the effect of congenital dyskeratosis 1 (DKC1) on neuroblastoma and its regulation mechanism.

Methods: The expression of DKC1 in neuroblastoma was analyzed by TCGA database and molecular assay. NB cells were transfected with siDKC1 to observe the effects of DKC1 on proliferation, cloning, metastasis, and invasion, and apoptosis and apoptosis-related proteins. The tumor-bearing mouse model was constructed, shDKC1 was transfected to observe the tumor growth and tumor tissue changes, and the expression of DKC1 and Ki-67 was detected. Screening and identification of miRNA326-5p targeting DKC1. NB cells were treated with miRNA326-5p mimic or inhibitors to detect the expression of DKC1. NB cells were transfected with miRNA326-5p and DKC1 mimics to detect cell proliferation, apoptosis, and apoptotic protein expression.

Results: DKC1 was highly expressed in NB cells and tissues. The activity, proliferation, invasion, and migration of NB cells were significantly decreased by DKC1 gene knockout, while apoptosis was significantly increased. The expression level of B-cell lymphoma-2 in shDKC1 group was significantly lower than that of the control group, while the expression level of BAK, BAX, and caspase-3 was significantly higher than that of the control group. The results of experiments on tumor-bearing mice were consistent with the above results. The results of miRNA assay showed that miRNA326-5p could bind DKC1 mRNA to inhibit the protein expression, thereby inhibiting the proliferation of NB cells, promoting their apoptosis, and regulating the expression of apoptotic proteins.

Conclusion: miRNA326-5p targeting DKC1 mRNA regulates apoptosis-related proteins to inhibit neuroblastoma proliferation and promote the apoptotic process.

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miRNA326-5p靶向DKC1基因以调节细胞凋亡相关蛋白并干预神经母细胞瘤的发展。
目的:探讨先天性角化不良1型(DKC1)对神经母细胞瘤的影响及其调控机制。方法:应用TCGA数据库和分子生物学方法分析DKC1在神经母细胞瘤中的表达。用siDKC1转染NB细胞,观察DKC1对增殖、克隆、转移和侵袭以及凋亡和凋亡相关蛋白的影响。构建荷瘤小鼠模型,转染shDKC1观察肿瘤生长和肿瘤组织变化,检测DKC1和Ki-67的表达。靶向DKC1的miRNA326-5p的筛选和鉴定。用miRNA326-5p模拟物或抑制剂处理NB细胞以检测DKC1的表达。用miRNA326-5p和DKC1模拟物转染NB细胞以检测细胞增殖、凋亡和凋亡蛋白表达。结果:DKC1在NB细胞和组织中高表达。DKC1基因敲除显著降低NB细胞的活性、增殖、侵袭和迁移,而凋亡显著增加。shDKC1组B细胞淋巴瘤-2的表达水平显著低于对照组,而BAK、BAX和胱天蛋白酶-3的表达水平明显高于对照组。对荷瘤小鼠的实验结果与上述结果一致。miRNA检测结果表明,miRNA326-5p可以结合DKC1mRNA抑制蛋白表达,从而抑制NB细胞的增殖,促进其凋亡,并调节凋亡蛋白的表达。结论:靶向DKC1 mRNA的miRNA326-5p调控细胞凋亡相关蛋白,抑制神经母细胞瘤的增殖,促进细胞凋亡过程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Analytical Cellular Pathology
Analytical Cellular Pathology ONCOLOGY-CELL BIOLOGY
CiteScore
4.90
自引率
3.10%
发文量
70
审稿时长
16 weeks
期刊介绍: Analytical Cellular Pathology is a peer-reviewed, Open Access journal that provides a forum for scientists, medical practitioners and pathologists working in the area of cellular pathology. The journal publishes original research articles, review articles, and clinical studies related to cytology, carcinogenesis, cell receptors, biomarkers, diagnostic pathology, immunopathology, and hematology.
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