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KIAA1429通过介导BTG2的m6A修饰在宫颈癌上皮-间质转化中的调控作用

The regulatory role of KIAA1429 in epithelial-mesenchymal transition in cervical cancer via mediating m6A modification of BTG2.

作者信息

Wang Mingyang, Wang Zhiliang, Zou Xiaofeng, Yang Danhe, Xu Ke

机构信息

Department of Gynecology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003 Guizhou China.

出版信息

Cytotechnology. 2025 Feb;77(1):34. doi: 10.1007/s10616-024-00694-3. Epub 2025 Jan 3.

Abstract

UNLABELLED

Cervical cancer (CC) represents one of the important cancers affecting global female population worldwide. We sought to elucidate the roles and mechanisms of KIAA1429 in the malignant properties of CC cells and the epithelial-mesenchymal transition (EMT) process. KIAA1429 was predicted to be abnormally expressed in CC and correlate with shortened survival of CC patients by GEPIA2 and GSCA databases. High expression of KIAA1429 in human CC cell lines (SiHa, HT-3) was validated by RT-qPCR and Western blot assays. A series of small interfering (si)RNAs including si-KIAA1429-1, si-KIAA1429-2, si-YTHDF2, si-BTG2, and si-negative control (NC) were utilized to interfere the expression levels of KIAA1429, YTHDF2, and BTG2, respectively. Consequently, KIAA1429 silencing attenuated the proliferation, migratory, and invasive functions of CC cells and repressed EMT while promoting CC cell apoptosis. Mechanistically, KIAA1429 could affect N6-methyladenosine (m6A) modification to attenuate the stability of BTG2 mRNA and down-regulate its expression. Additionally, loss of BTG2 partly counteracted the effects of si-KIAA1429 on repressing the malignant activities of CC cells. The aforementioned results collectively demonstrated that KIAA1429-mediated m6A modification of BTG2 and contributed to malignant progression of CC in vitro.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s10616-024-00694-3.

摘要

未标记

宫颈癌(CC)是影响全球女性人口的重要癌症之一。我们试图阐明KIAA1429在CC细胞恶性特性和上皮-间质转化(EMT)过程中的作用及机制。通过GEPIA2和GSCA数据库预测,KIAA1429在CC中异常表达,并与CC患者生存期缩短相关。通过RT-qPCR和蛋白质免疫印迹分析验证了KIAA1429在人CC细胞系(SiHa、HT-3)中的高表达。分别使用一系列小干扰(si)RNA,包括si-KIAA1429-1、si-KIAA1429-2、si-YTHDF2、si-BTG2和si阴性对照(NC)来干扰KIAA1429、YTHDF2和BTG2的表达水平。因此,沉默KIAA1429可减弱CC细胞的增殖、迁移和侵袭功能,抑制EMT,同时促进CC细胞凋亡。机制上,KIAA1429可影响N6-甲基腺苷(m6A)修饰,以减弱BTG2 mRNA的稳定性并下调其表达。此外,BTG2的缺失部分抵消了si-KIAA1429对抑制CC细胞恶性活性的影响。上述结果共同表明,KIAA1429介导的BTG2的m6A修饰促进了CC的体外恶性进展。

补充信息

在线版本包含可在10.1007/s10616-024-00694-3获取的补充材料。

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