LncRNA 在癌症进展和靶向中发挥着至关重要的作用，但识别结直肠癌 (CRC) 进展中涉及的关键 lncRNA 一直很困难。我们使用 21 对 IV 期 CRC 组织和邻近正常组织，将 FAM83H-AS1 鉴定为肿瘤促进相关 lncRNA。体外和体内实验表明，CRC细胞中FAM83H-AS1的敲低可抑制肿瘤增殖和转移，反之亦然。 m6A 修饰对于通过写入器 METTL3 和读取器 IGF2BP2/IGFBP3 的 FAM83H-AS1 RNA 稳定性至关重要。 PTBP1（一种 RNA 结合蛋白）负责 CRC 中的 FAM83H-AS1 功能。 FAM83H-AS1 外显子 4 上的 T4 (1770-2440nt) 和 T5 (2440-2743nt) 为 PTBP1 RRM2 相互作用提供平台。我们的结果表明，m6A 修饰通过磷酸化 PTBP1 对其 RNA 剪接作用来失调 FAM83H-AS1 的致癌作用。在患者来源的异种移植模型中，ASO-FAM83H-AS1 显着抑制胃肠道 (GI) 肿瘤的生长，不仅包括 CRC，还包括 GC 和 ESCC。与单独使用任一药物治疗相比，ASO-FAM83H-AS1 和奥沙利铂/顺铂的组合显着抑制了肿瘤生长。值得注意的是，这三种胃肠道癌症均出现病理学完全缓解。我们的研究结果表明，FAM83H-AS1 靶向治疗将使主要接受铂类治疗的胃肠道癌症患者受益。版权所有 © 2024。由 Elsevier B.V. 出版。

LncRNA plays a crucial role in cancer progression and targeting, but it has been difficult to identify the critical lncRNAs involved in colorectal cancer (CRC) progression. We identified FAM83H-AS1 as a tumor-promoting associated lncRNA using 21 pairs of stage IV CRC tissues and adjacent normal tissues. In vitro and in vivo experiments revealed that knockdown of FAM83H-AS1 in CRC cells inhibited tumor proliferation and metastasis, and vice versa. m6A modification is critical for FAM83H-AS1 RNA stability through the writer METTL3 and the readers IGF2BP2/IGFBP3. PTBP1-an RNA binding protein-is responsible for the FAM83H-AS1 function in CRC. T4 (1770-2440nt) and T5 (2440-2743nt) on exon 4 of FAM83H-AS1 provide a platform for PTBP1 RRM2 interactions. Our results demonstrated that m6A modification dysregulated the FAM83H-AS1 oncogenic role by phosphorylated PTBP1 on its RNA splicing effect. In patient-derived xenograft models, ASO-FAM83H-AS1 significantly suppressed the growth of gastrointestinal (GI) tumors, not only CRC but also GC and ESCC. The combination of ASO-FAM83H-AS1 and oxaliplatin/cisplatin significantly suppressed tumor growth compared with treatment with either agent alone. Notably, there was pathological complete response in all these three GI cancers. Our findings suggest that FAM83H-AS1 targeted therapy would benefit patients primarily receiving platinum-based therapy in GI cancers.Copyright © 2024. Published by Elsevier B.V.