Feng Xi, Shu Liuping
Department of Gynecology, Wujin Hospital Affiliated with Jiangsu University; The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, PR China.
Histol Histopathol. 2024 Nov 4:18843. doi: 10.14670/HH-18-843.
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 . 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.
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CC潜在的分子机制了解不足。本研究旨在探讨KIAA1429（VIRMA，类病毒m6A甲基转移酶相关蛋白）在CC患者中的预后价值，并分析其分子机制。采用RT-qPCR和蛋白质免疫印迹法检测肿瘤标本中KIAA1429的水平。使用CCK-8和Transwell实验评估细胞生物学过程。通过异种移植实验验证KIAA1429在CC中的功能。结果表明，CC中KIAA1429表达增强。下调KIAA1429可抑制CC细胞的活力、迁移和侵袭。此外，发现LARP1（La相关蛋白1）受KIAA1429正向调控。此外，LARP1扩增可抵消KIAA1429缺失对CC细胞表型的抗肿瘤作用。此外，KIAA1429缺陷通过甲基化LARP1抑制其稳定性。总体而言，KIAA1429可通过m6A甲基化修饰LARP1以促进其稳定性，从而促进CC的肿瘤发生。这项工作突出了KIAA1429对CC发展的促进作用，并为其治疗提供了新的靶点。
