The methyltransferase KIAA1429 potentiates cervical cancer tumorigenesis via modulating LARP1 mRNA m6A modification and stability.

IF 2.5 4区 生物学 Q3 CELL BIOLOGY
Xi Feng, Liuping Shu
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引用次数: 0

Abstract

Cervical cancer (CC) is one of the most common gynecological malignancies in the world and poses a great threat to public health. There is inadequate knowledge of the molecular mechanisms underlying CC. This study aimed to explore the prognostic value of KIAA1429 (VIRMA, vir-Like m6A methyltransferase associated) in patients with CC and analyze its molecular mechanisms. The level of KIAA1429 in tumor specimens was tested using RT-qPCR and western blotting. Cellular biological processes were assessed using CCK-8 and Transwell assays. Xenograft experiments were used to verify the function of KIAA1429 in CC in vivo. The results manifested that KIAA1429 expression was enhanced in CC. Downregulation of KIAA1429 hindered the viability, migration, and invasion of CC cells. Moreover, LARP1 (La-related protein 1) was uncovered to be positively modulated by KIAA1429. Further, the anti-tumor impacts of KIAA1429 depletion on the phenotype of CC cells were counteracted by LARP1 amplification. Additionally, KIAA1429 deficiency suppressed the stability of LARP1 through methylating LARP1. Collectively, KIAA1429 can boost the tumorigenesis of CC via modifying LARP1 through m6A methylation to promote its stability. This work highlights the promoting effects of KIAA1429 on CC development and presents new targets for its treatment.

甲基转移酶KIAA1429通过调节LARP1 mRNA m6A的修饰和稳定性而促进宫颈癌的发生。
宫颈癌(CC)是世界上最常见的妇科恶性肿瘤之一,对公众健康构成巨大威胁。目前对宫颈癌的分子机制还缺乏足够的了解。本研究旨在探讨KIAA1429(VIRMA,vir-Like m6A甲基转移酶相关)在CC患者中的预后价值,并分析其分子机制。研究采用RT-qPCR和Western印迹法检测了肿瘤标本中KIAA1429的水平。使用 CCK-8 和 Transwell 试验评估细胞生物学过程。异种移植实验用于验证 KIAA1429 在体内 CC 中的功能。结果表明,KIAA1429在CC中的表达增强。下调KIAA1429会阻碍CC细胞的活力、迁移和侵袭。此外,还发现LARP1(La相关蛋白1)受KIAA1429的正向调节。此外,KIAA1429的缺失对CC细胞表型的抗肿瘤影响被LARP1的扩增所抵消。此外,KIAA1429的缺乏还通过甲基化LARP1抑制了LARP1的稳定性。总之,KIAA1429可通过m6A甲基化修饰LARP1,促进其稳定性,从而促进CC的肿瘤发生。这项研究强调了KIAA1429对CC发展的促进作用,并提出了治疗CC的新靶点。
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
Histology and histopathology
Histology and histopathology 生物-病理学
CiteScore
3.90
自引率
0.00%
发文量
232
审稿时长
2 months
期刊介绍: HISTOLOGY AND HISTOPATHOLOGY is a peer-reviewed international journal, the purpose of which is to publish original and review articles in all fields of the microscopical morphology, cell biology and tissue engineering; high quality is the overall consideration. Its format is the standard international size of 21 x 27.7 cm. One volume is published every year (more than 1,300 pages, approximately 90 original works and 40 reviews). Each volume consists of 12 numbers published monthly online. The printed version of the journal includes 4 books every year; each of them compiles 3 numbers previously published online.
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