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

Cell Death Dis. 2024 Sep 3;15(9):645. doi: 10.1038/s41419-024-06958-2.

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.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Disease Progression*
  • Female
  • Forkhead Transcription Factors* / genetics
  • Forkhead Transcription Factors* / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Glycolysis / genetics
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Male
  • Metabolic Reprogramming
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism

Substances

  • MicroRNAs
  • MIRN141 microRNA, human
  • Forkhead Transcription Factors
  • RNA, Long Noncoding
  • long noncoding RNA HIF1A-AS2, human
  • Sp1 Transcription Factor
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • SP1 protein, human