Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of digestive Disease, Fourth Military Medical University, Xi'an, 710032, China.
Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Cancer Lett. 2024 Aug 1;596:217004. doi: 10.1016/j.canlet.2024.217004. Epub 2024 Jun 3.
Long non-coding RNA (lncRNA) is closely related to a variety of human cancers, which may provide huge potential biomarkers for cancer diagnosis and treatment. However, the aberrant expression of most lncRNAs in colorectal cancer (CRC) remains elusive. This study aims to explore the clinical significance and potential mechanism of lncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) in the colorectal cancer. Here, we demonstrated that lncRNA ABHD11-AS1 is high-expressed in colorectal cancer (CRC) patients, and strongly related with poor prognosis. Functionally, ABHD11-AS1 suppresses ferroptosis and promotes proliferation and migration in CRC both in vitro and in vivo. Mechanically, lncRNA ABHD11-AS1 interacted with insulin-like growing factor 2 mRNA-binding protein 2 (IGF2BP2) to enhance FOXM1 stability, forming an ABHD11-AS1/FOXM1 positive feedback loop. E3 ligase tripartite motif containing 21 (TRIM21) promotes the degradation of IGF2BP2 via the K48-ubiquitin-lysosome pathway and ABHD11-AS1 promotes the interaction between IGF2BP2 and TRIM21 as scaffold platform. Furthermore, N -adenosine-methyltransferase-like 3 (METTL3) upregulated the stabilization of ABHD11-AS1 through the mA reader IGF2BP2. Our study highlights ABHD11-AS1 as a significant regulator in CRC and it may become a potential target in future CRC treatment.
长链非编码 RNA（lncRNA）与多种人类癌症密切相关，可能为癌症的诊断和治疗提供巨大的潜在生物标志物。然而，大多数 lncRNA 在结直肠癌（CRC）中的异常表达仍难以捉摸。本研究旨在探讨 lncRNA ABHD11 反义 RNA 1（ABHD11-AS1）在结直肠癌中的临床意义和潜在机制。在这里，我们证明 lncRNA ABHD11-AS1 在结直肠癌（CRC）患者中高表达，并与预后不良密切相关。功能上，ABHD11-AS1 在体外和体内均抑制铁死亡并促进 CRC 的增殖和迁移。机制上，lncRNA ABHD11-AS1 与胰岛素样生长因子 2 mRNA 结合蛋白 2（IGF2BP2）相互作用，增强 FOXM1 的稳定性，形成 ABHD11-AS1/FOXM1 正反馈环。E3 连接酶三部分基序包含 21 个（TRIM21）通过 K48-泛素-溶酶体途径促进 IGF2BP2 的降解，ABHD11-AS1 作为支架平台促进 IGF2BP2 和 TRIM21 之间的相互作用。此外，N -腺苷甲硫氨酸转移酶样 3（METTL3）通过 mA 阅读器 IGF2BP2 上调 ABHD11-AS1 的稳定性。我们的研究强调了 ABHD11-AS1 作为 CRC 的重要调节剂，它可能成为未来 CRC 治疗的潜在靶点。
