Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College Fudan University, Shanghai, China.
Cell Death Dis. 2024 Sep 3;15(9):645. doi: 10.1038/s41419-024-06958-2.
lncRNA can regulate tumorigenesis development and distant metastasis of colorectal cancer (CRC). However, the detailed molecular mechanisms are still largely unknown. Using RNA-sequencing data, RT-qPCR, and FISH assay, we found that HIF1A-AS2 was upregulated in CRC tissues and associated with poor prognosis. Functional experiments were performed to determine the roles of HIF1A-AS2 in tumor progression and we found that HIF1A-AS2 can promote the proliferation, metastasis, and aerobic glycolysis of CRC cells. Mechanistically, HIF1A-AS2 can promote FOXC1 expression by sponging miR-141-3p. SP1 can transcriptionally activate HIF1A-AS2. Further, HIF1A-AS2 can be packaged into exosomes and promote the malignant phenotype of recipient tumor cells. Taken together, we discovered that SP1-induced HIF1A-AS2 can promote the metabolic reprogramming and progression of CRC via miR-141-3p/FOXC1 axis. HIF1A-AS2 is a promising diagnostic marker and treatment target in CRC.
长链非编码 RNA（lncRNA）可调节结直肠癌（CRC）的发生发展和远处转移。然而，其详细的分子机制在很大程度上尚不清楚。本研究通过 RNA 测序数据、RT-qPCR 和 FISH 检测发现，HIF1A-AS2 在 CRC 组织中上调，并与不良预后相关。功能实验确定了 HIF1A-AS2 在肿瘤进展中的作用，结果表明 HIF1A-AS2 可促进 CRC 细胞的增殖、转移和有氧糖酵解。机制上，HIF1A-AS2 通过海绵吸附 miR-141-3p 促进 FOXC1 的表达。SP1 可转录激活 HIF1A-AS2。此外，HIF1A-AS2 可被包装到外泌体中，并促进受体肿瘤细胞的恶性表型。综上所述，本研究发现，SP1 诱导的 HIF1A-AS2 通过 miR-141-3p/FOXC1 轴促进 CRC 的代谢重编程和进展。HIF1A-AS2 是 CRC 有前途的诊断标志物和治疗靶点。
