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环状 RNA KIAA0368 通过上调鼻咽癌中 HOXA10 的表达促进增殖、迁移和侵袭。

CircKIAA0368 Promotes Proliferation, Migration, and Invasion by Upregulating HOXA10 in Nasopharyngeal Carcinoma.

机构信息

Department of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, China.

Department of Radiation Oncology, 146391Jiangxi Cancer Hospital, Nanchang, China.

出版信息

Am J Rhinol Allergy. 2022 Sep;36(5):615-627. doi: 10.1177/19458924221100960. Epub 2022 May 20.

DOI:10.1177/19458924221100960
PMID:35593126
Abstract

BACKGROUND

Nasopharyngeal carcinoma (NPC) represents a head and neck cancer caused by cancerization of nasal epithelial cells. HOXA10 has been identified to promote proliferation and invasion of NPC cells, but its regulatory mechanism has not been well discussed. Published research work has also pointed out that circular RNAs (circRNAs) could regulate mRNAs to affect NPC tumorigenesis and development.

AIM

To explore the roles of HOXA10 and its specific regulatory mechanism regarding circRNAs in NPC.

METHODS

Reverse transcription polymerase chain reaction and western blot were applied to test gene expression. Functional assays were used to evaluate changes in NPC cell phenotypes. Mechanism assays were done to verify RNA-RNA or RNA-protein interaction.

RESULTS

HOXA10 was highly expressed in NPC tissues and cell lines. Moreover, HOXA10 knockdown could restrict NPC cell proliferation, invasion, migration, and epithelial-mesenchymal transition. CircKIAA0368 was upregulated in NPC cells and could elevate HOXA10 expression by sponging miR-6838-5p. Furthermore, circKIAA0368 was unveiled to competitively bind to p300/CREB-binding protein-associated factor (PCAF) to repress acetylation and degradation of HOXA10 protein.

CONCLUSION

CircKIAA0368 upregulates HOXA10 expression via miR-6838-5p and PCAF, consequently promoting NPCcell and tumor growth.

摘要

背景

鼻咽癌(NPC)是一种由鼻上皮细胞癌变引起的头颈部癌症。HOXA10 已被确定可促进 NPC 细胞的增殖和侵袭,但它的调节机制尚未得到很好的讨论。已发表的研究工作还指出,环状 RNA(circRNA)可以调节 mRNAs,从而影响 NPC 肿瘤的发生和发展。

目的

探讨 HOXA10 及其在 NPC 中circRNA 特定调节机制的作用。

方法

采用逆转录聚合酶链反应和 Western blot 检测基因表达。功能测定用于评估 NPC 细胞表型的变化。机制测定用于验证 RNA-RNA 或 RNA-蛋白相互作用。

结果

HOXA10 在 NPC 组织和细胞系中高表达。此外,HOXA10 敲低可限制 NPC 细胞的增殖、侵袭、迁移和上皮-间充质转化。circKIAA0368 在 NPC 细胞中上调,并可通过海绵 miR-6838-5p 来提高 HOXA10 的表达。此外,circKIAA0368 被揭示可竞争性结合 p300/CREB 结合蛋白相关因子(PCAF),从而抑制 HOXA10 蛋白的乙酰化和降解。

结论

circKIAA0368 通过 miR-6838-5p 和 PCAF 上调 HOXA10 的表达,从而促进 NPC 细胞和肿瘤的生长。

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Am J Rhinol Allergy. 2022 Sep;36(5):615-627. doi: 10.1177/19458924221100960. Epub 2022 May 20.
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