Cell Death and Disease (Sep 2024)

HIF1A-AS2 promotes the metabolic reprogramming and progression of colorectal cancer via miR-141-3p/FOXC1 axis

  • 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

DOI
https://doi.org/10.1038/s41419-024-06958-2
Journal volume & issue
Vol. 15, no. 9
pp. 1 – 18

Abstract

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Abstract 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.