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KIAA1429介导的ZFPM2-AS1 mA修饰促进骨肉瘤细胞的增殖、迁移和侵袭。

KIAA1429-mediated ZFPM2-AS1 mA modification promotes the proliferation, migration and invasion of osteosarcoma cells.

作者信息

Zhang Yuanzhuang, Bao Yuxin, Zhai Hanjie, Li Chenghao, Shi Hongchao, Gong Keyang, Bao Xiaohe

机构信息

Fourth Department of Orthopedic Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China.

School of Basic Medicine, Shenyang Medical College, Shenyang, Liaoning 110000, P.R. China.

出版信息

Oncol Lett. 2025 Jul 21;30(4):453. doi: 10.3892/ol.2025.15199. eCollection 2025 Oct.

Abstract

Osteosarcoma is the most prevalent malignant bone tumor in pediatric and adolescent populations. N-methyladenosine (mA) is a post-transcriptional modification of RNA, and the most prevalent internal chemical modification of mRNA. KIAA1429, also known as virus-like mA methyltransferase-associated, is a key component of the mA methyltransferase complex, and the largest protein within this complex. Long non-coding RNAs (lncRNAs) are a class of transcripts >200 nucleotides in length that are able to regulate gene expression. Friend of GATA family member 2-antisense 1 (ZFPM2-AS1) is a lncRNA that has been observed to exhibit aberrantly elevated expression in gastric cancer. The present study aimed to explore the expression levels of KIAA1429 and ZFPM2-AS1 in osteosarcoma tissues and 143B and MG63 osteosarcoma cell lines. The results of bioinformatics analysis, reverse transcription-quantitative PCR (qPCR) and western blotting revealed that the expression of KIAA1429 and ZFPM2-AS1 in osteosarcoma tissues and cell lines was upregulated compared with that in the corresponding normal tissues or cells. The association between KIAA1429-mediated mA modifications and ZFPM2-AS1 stability in osteosarcoma cells was confirmed using mA-methylated RNA immunoprecipitation-qPCR and actinomycin D assays. In addition, in Cell Counting Kit-8 and Transwell assays KIAA1429 overexpression promoted the proliferation, invasion and migration of 143B and MG63 osteosarcoma cells, and these promotive effects were attenuated by ZFPM2-AS1 knockdown. These findings suggest a potential novel approach for molecular therapy in the treatment of osteosarcoma.

摘要

骨肉瘤是儿童和青少年中最常见的恶性骨肿瘤。N6-甲基腺苷(m6A)是RNA的一种转录后修饰,也是mRNA中最常见的内部化学修饰。KIAA1429,也称为病毒样m6A甲基转移酶相关蛋白,是m6A甲基转移酶复合物的关键组成部分,也是该复合物中最大的蛋白质。长链非编码RNA(lncRNA)是一类长度大于200个核苷酸的转录本,能够调节基因表达。GATA家族成员2反义1(ZFPM2-AS1)是一种lncRNA,已观察到其在胃癌中异常高表达。本研究旨在探讨KIAA1429和ZFPM2-AS1在骨肉瘤组织以及143B和MG63骨肉瘤细胞系中的表达水平。生物信息学分析、逆转录定量PCR(qPCR)和蛋白质印迹结果显示,与相应的正常组织或细胞相比,KIAA1429和ZFPM2-AS1在骨肉瘤组织和细胞系中的表达上调。使用m6A甲基化RNA免疫沉淀-qPCR和放线菌素D试验证实了骨肉瘤细胞中KIAA1429介导的m6A修饰与ZFPM2-AS1稳定性之间的关联。此外,在细胞计数试剂盒-8和Transwell试验中,KIAA1429过表达促进了143B和MG63骨肉瘤细胞的增殖、侵袭和迁移,而ZFPM2-AS1敲低减弱了这些促进作用。这些发现提示了一种治疗骨肉瘤的潜在新分子治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/618c/12311418/1496d1225c91/ol-30-04-15199-g00.jpg

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