Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear. The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT–PCR and FISH. In vitro and in vivo experiments, such as BODIPY staining, Oil Red O staining, triglyceride (TAG) assays, and liquid chromatography mass spectrometry (LC-MS) were subsequently performed with CRC specimens and cells to determine the clinical significance, and functional roles of POU6F2-AS1. Biotinylated RNA pull-down, RIP, Me-RIP, ChIP, and patient-derived organoid (PDO) culture assays were performed to confirm the underlying mechanism of POU6F2-AS1. The lncRNA POU6F2-AS1 is markedly upregulated in CRC and associated with adverse clinicopathological features and poor overall survival in CRC patients. Functionally, POU6F2-AS1 promotes the growth and lipogenesis of CRC cells both in vitro and in vivo. Mechanistically, METTL3-induced m6A modification is involved in the upregulation of POU6F2-AS1. Furthermore, upregulated POU6F2-AS1 could tether YBX1 to the FASN promoter to induce transcriptional activation, thus facilitating the growth and lipogenesis of CRC cells. Our data revealed that the upregulation of POU6F2-AS1 plays a critical role in CRC fatty acid metabolism and might provide a novel promising biomarker and therapeutic target for CRC.

中文翻译：

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m6A修饰介导的lncRNA POU6F2-AS1重新编程脂肪酸代谢并通过上调FASN促进结直肠癌的生长

长非编码 RNA (lncRNA) 已成为肿瘤发生和肿瘤进展的关键参与者。然而，lncRNA在结直肠癌（CRC）中的生物学功能和潜在机制尚不清楚。通过生物信息学分析鉴定出新型lncRNA POU6F2-AS1，并通过qRT-PCR和FISH验证其在CRC患者中的表达。随后对 CRC 标本和细胞进行体外和体内实验，例如 BODIPY 染色、油红 O 染色、甘油三酯 (TAG) 测定和液相色谱质谱 (LC-MS)，以确定临床意义和功能作用POU6F2-AS1。进行了生物素化 RNA Pull-down、RIP、Me-RIP、ChIP 和患者来源的类器官 (PDO) 培养测定，以确认 POU6F2-AS1 的潜在机制。lncRNA POU6F2-AS1 在 CRC 中显着上调，并与 CRC 患者不良的临床病理特征和较差的总生存率相关。从功能上讲，POU6F2-AS1 在体外和体内均可促进 CRC 细胞的生长和脂肪生成。从机制上讲，METTL3 诱导的 m6A 修饰参与 POU6F2-AS1 的上调。此外，上调的 POU6F2-AS1 可以将 YBX1 与 FASN 启动子连接，诱导转录激活，从而促进 CRC 细胞的生长和脂肪生成。我们的数据显示，POU6F2-AS1 的上调在 CRC 脂肪酸代谢中发挥着关键作用，可能为 CRC 提供新的有前景的生物标志物和治疗靶点。