ALYREF stabilizes CREPT mRNA to accelerate the development of nasopharyngeal carcinoma through dependence on m5C modification

IF 3.5 3区 生物学 Q3 CELL BIOLOGY
Danni Xu , Yu Fu , Huamao Sun , Yanda Lu , Bo Shen , Xinbao Hao
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引用次数: 0

Abstract

Background

Nasopharyngeal carcinoma (NPC) is a kind of tumor disease with high malignant degree. CREPT expression was elevated abnormally in multi-cancers. However, the role and regulatory mechanism of CREPT in NPC remains unknown.

Methods

NPC clinical samples, NPC cells, and nude mice served as experimental objects. The levels of molecules were detected using RT-qPCR,Western blot, IF and IHC experiments. Malignant activities of NPC cells were evaluated using CCK-8, EdU and clone formation, flow cytometry and TUNEL. Kaplan-Meier and Pearson correlation analysis were employed to analysis of the relationships between CREPT expression and prognosis/ALYREF expression in NPC patients. The interaction between ALYREF and CREPT was validated using RIP, RNA pull-down and dual luciferase experiment.

Results

Upregulation of CREPT and ALYREF expression was observed in NPC samples including the tissues of NPC patients and cells. CREPT knockdown reduced NPC cell viability, proliferation and enhanced NPC cell apoptosis and suppressed tumor growth through deactivating Wnt/β-catenin pathway, but the results of ALYREF overexpression had the inverse results of CREPT knockdown. Furthermore, the combination of CREPT knockdown and ALYREF overexpression compromised ALYREF overexpression-mediated the influences on NPC cells, tumor growth and motivating Wnt/β-catenin pathway. Furthermore, ALYREF interacted with CREPT mRNA and ALYREF promoted the stability of CREPT mRNA in m5C-dependent manner.

Conclusion

ALYREF stabilized CREPT mRNA through interacting with m5C-labeled CREPT mRNA to elevate CREPT expression, thus activating Wnt/β-catenin pathway and facilitating NPC progression.
ALYREF通过依赖m5C修饰稳定了悄悄mRNA,加速鼻咽癌的发展。
背景:鼻咽癌是一种恶性程度较高的肿瘤疾病。在多种肿瘤中,蹑手蹑脚的表达异常升高。然而,在NPC中的作用和调控机制尚不清楚。方法:以鼻咽癌临床标本、鼻咽癌细胞和裸鼠为实验对象。采用RT-qPCR、western blot、IF和IHC实验检测分子水平。采用CCK-8、EdU、克隆形成、流式细胞术和TUNEL技术评价鼻咽癌细胞的恶性活性。应用Kaplan-Meier和Pearson相关分析分析鼻咽癌患者中悄悄表达与预后/ALYREF表达的关系。通过RIP、RNA下拉和双荧光素酶实验验证ALYREF与creep的相互作用。结果:在鼻咽癌患者组织和细胞中,观察到蹑网膜和ALYREF的表达上调。通过灭活Wnt/β-catenin通路,降低鼻咽癌细胞活力、增殖,增强鼻咽癌细胞凋亡,抑制肿瘤生长,而ALYREF过表达的结果与蹑关节敲低的结果相反。此外,低敲除和ALYREF过表达联合抑制了ALYREF过表达介导的对鼻咽癌细胞、肿瘤生长和激活Wnt/β-catenin通路的影响。此外,ALYREF与悄悄mRNA相互作用,ALYREF以m5c依赖的方式促进悄悄mRNA的稳定性。结论:ALYREF通过与m3c标记的悄悄mRNA相互作用,稳定悄悄mRNA的表达,从而激活Wnt/β-catenin通路,促进鼻咽癌进展。
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
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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