HIF1A-AS2 通过 miR-141-3p/FOXC1 轴促进结直肠癌的代谢重编程和进展。
HIF1A-AS2 promotes the metabolic reprogramming and progression of colorectal cancer via miR-141-3p/FOXC1 axis.
发表日期:2024 Sep 03
作者:
Xinyang Zhong, Yaxian Wang, Xuefeng He, Xinxin He, Zijuan Hu, Huixia Huang, Jiayu Chen, Keji Chen, Ping Wei, Senlin Zhao, Yilin Wang, Hong Zhang, Bo Feng, Dawei Li
来源:
Cell Death & Disease
摘要:
lncRNA可以调控结直肠癌(CRC)的肿瘤发生发展和远处转移。然而,详细的分子机制仍然很大程度上未知。利用 RNA 测序数据、RT-qPCR 和 FISH 检测,我们发现 HIF1A-AS2 在 CRC 组织中表达上调,并且与不良预后相关。通过功能实验确定 HIF1A-AS2 在肿瘤进展中的作用,我们发现 HIF1A-AS2 可以促进 CRC 细胞的增殖、转移和有氧糖酵解。从机制上讲,HIF1A-AS2 可以通过海绵 miR-141-3p 促进 FOXC1 表达。 SP1 可以转录激活 HIF1A-AS2。此外,HIF1A-AS2可以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,我们发现 SP1 诱导的 HIF1A-AS2 可以通过 miR-141-3p/FOXC1 轴促进 CRC 的代谢重编程和进展。 HIF1A-AS2 是 CRC 中一种有前景的诊断标记物和治疗靶点。© 2024。作者。
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.© 2024. The Author(s).