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KIAA1429通过调控CA9的m6A甲基化促进口腔鳞状细胞癌的恶性发展。

KIAA1429 promotes the malignancy of oral squamous cell carcinoma by regulating CA9 m6A methylation.

作者信息

Tu Jia, Feng Xiao, Cao Qingqing, Guan Yan

机构信息

Department of Stomatology, Hubei Provincial Hospital of Traditional Chinese Medicine, Hongshan District, No. 856, Luoyu Road, Wuhan, 430061 Hubei China.

出版信息

Cytotechnology. 2024 Oct;76(5):585-594. doi: 10.1007/s10616-024-00640-3. Epub 2024 Jul 9.

DOI:10.1007/s10616-024-00640-3
PMID:39188646
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11344743/
Abstract

UNLABELLED

KIAA1429 has been reported as a cancer regulator, but its role and mechanism in the progression of oral squamous cell carcinoma (OSCC) remain elusive. The objective of the present research was to figure out the effect of KIAA1429 regulated CA9 on the progression of OSCC. Using qRT-PCR and bioinformatics analysis, we studied the expression levels of KIAA1429 and CA9 in OSCC tissue samples. The functional roles of KIAA1429 and CA9 were assessed using transwell and CCK-8 assays. The regulation among KIAA1429 and CA9 was investigated using MeRIP and western blotting assays. In addition, the m6A level in OSCC was measured utilizing RNA m6A quantification. In OSCC, KIAA1429 and m6A levels were upregulated. We observed that KIAA1429 inhibition declined proliferation, migration, and invasion of OSCC cells and decreased cell growth in vivo. Furthermore, KIAA1429 serves as a crucial upstream regulator of CA9 in OSCC and upregulates CA9 expression through an m6A-dependent mechanism. We observed that CA9 was upregulated in OSCC samples and that low expression of KIAA1429 partially restored the enhanced malignant phenotype caused by CA9 overexpression. Overall, our findings suggest that KIAA1429 and CA9 act as pro-oncogenic factors in OSCC, with KIAA1429 promoting OSCC malignancy through m6A modification-dependent stabilization of CA9 transcripts, which represents a novel regulatory mechanism in OSCC.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s10616-024-00640-3.

摘要

未标注

KIAA1429已被报道为一种癌症调节因子,但其在口腔鳞状细胞癌(OSCC)进展中的作用和机制仍不清楚。本研究的目的是弄清楚KIAA1429调控的CA9对OSCC进展的影响。通过qRT-PCR和生物信息学分析,我们研究了OSCC组织样本中KIAA1429和CA9的表达水平。使用Transwell和CCK-8实验评估KIAA1429和CA9的功能作用。使用MeRIP和蛋白质印迹实验研究KIAA1429和CA9之间的调控关系。此外,利用RNA m6A定量法测量OSCC中的m6A水平。在OSCC中,KIAA1429和m6A水平上调。我们观察到抑制KIAA1429可降低OSCC细胞的增殖、迁移和侵袭,并在体内减少细胞生长。此外,KIAA1429在OSCC中作为CA9的关键上游调节因子,并通过m6A依赖性机制上调CA9表达。我们观察到CA9在OSCC样本中上调,并且KIAA1429的低表达部分恢复了由CA9过表达引起的增强的恶性表型。总体而言,我们的研究结果表明,KIAA1429和CA9在OSCC中作为促癌因子发挥作用,KIAA1429通过m6A修饰依赖性稳定CA9转录本来促进OSCC恶性肿瘤发生,这代表了OSCC中的一种新的调控机制。

补充信息

在线版本包含可在10.1007/s10616-024-00640-3获取的补充材料。

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