Liu Huijun, Yang Menghan, Zhang Chunyue, Zhang Yanmin, Wang Yan, Chen Yueda
School of Public Health, Puyang Medical College, Puyang, 457000, China.
Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
Hereditas. 2025 Mar 11;162(1):34. doi: 10.1186/s41065-025-00393-9.
The screening and monitoring of gastric cancer is still a clinical challenge. Both N-methyladenosine (mA) and lncRNAs have been evidenced as critical regulators of gastric cancer, but their interaction and potential in modulating tumor progression remain unclear. This study aimed to evaluate the function of lncRNA LINC00968 in gastric cancer biological processes, and we discovered the role of KIAA1429, a typical mA eraser, in mediating LINC00968 function.
The expression of LINC00968 was assessed using PCR and regulated by cell transfection. Cellular processes were evaluated by CCK8 and Transwell assays. The mA modification and the interaction of LINC00968 with KIAA1429 were identified with Methylated RNA immunoprecipitation-qPCR. The regulatory effect of LINC00968 on miR-3202 and VIRMA was estimated by luciferase reporter assay.
Significantly increased LINC00968 was observed in gastric cancer cells. Silencing LINC00968 suppressed gastric cancer cell growth and motility. mA-modified sites were predicted in LINC00968 and overexpressing KIAA1429 enhanced the enrichment and stability of LINC00968 in gastric cancer and reversed the knockdown of LINC00968. The overexpression of KIAA1429 could attenuate the inhibitory effect of LINC00968 knockdown on gastric cancer cellular processes. LINC00968 could negatively regulate the expression of miR-3202, which further regulate VIRMA, the coding gene of KIAA1429, in gastric cancer cells.
LINC00968 contributes to the enhanced cell growth and metastasis of gastric cancer, which was mediated by KIAA1429-mediating mA modification and the miR-3202/VIRMA axis.
胃癌的筛查和监测仍然是一项临床挑战。N-甲基腺苷（mA）和长链非编码RNA（lncRNAs）均已被证明是胃癌的关键调节因子，但其相互作用以及在调节肿瘤进展方面的潜力仍不清楚。本研究旨在评估lncRNA LINC00968在胃癌生物学过程中的功能，并且我们发现了典型的mA去甲基化酶KIAA1429在介导LINC00968功能中的作用。
使用聚合酶链反应（PCR）评估LINC00968的表达，并通过细胞转染进行调控。通过细胞计数试剂盒-8（CCK8）和Transwell实验评估细胞过程。采用甲基化RNA免疫沉淀-定量聚合酶链反应（Methylated RNA immunoprecipitation-qPCR）鉴定LINC00968的mA修饰以及LINC00968与KIAA1429的相互作用。通过荧光素酶报告基因实验评估LINC00968对miR-3202和VIRMA的调控作用。
在胃癌细胞中观察到LINC00968显著上调。沉默LINC00968可抑制胃癌细胞的生长和迁移能力。在LINC00968中预测到了mA修饰位点，过表达KIAA1429可增强LINC00968在胃癌中的富集和稳定性，并逆转LINC00968的敲低。KIAA1429的过表达可减弱LINC00968敲低对胃癌细胞过程的抑制作用。在胃癌细胞中，LINC00968可负向调节miR-3202的表达，而miR-3202可进一步调节KIAA1429的编码基因VIRMA。
LINC00968促进胃癌细胞生长和转移增强，这是由KIAA1429介导的mA修饰以及miR-3202/VIRMA轴介导的。
