Skip to main content
Fig. 1 | Journal of Experimental & Clinical Cancer Research

Fig. 1

From: Noncoding RNAs as sensors of tumor microenvironmental stress

Fig. 1

The graphical representation of the HIFs-mediated regulatory mechanisms of ncRNA transcription upon hypoxia in TME. Under normoxia, HIFα subunit is hydroxylated by PHDs. Upon hydroxylation, HIFα interacts and binds to the VHL protein, which acts as a ubiquitin E3 ligase, eventually leading to proteasomal degradation of HIFα. FIH hydroxylates HIFα and halts its binding to CBP/p300. Upon hypoxia, oxygen depletion inhibits the hydroxylation of PHDs and FIH to promote HIFα stabilization and nucleus translocation. HIFα dimerizes with HIF-1β, recruits coactivator CBP/p300, and then binds to the HREs of target genes to regulate the transcription of various ncRNAs. Additionally, in hypoxic TME, HIFs upregulate multiple chromatin-modifying enzymes such as HDAC1/HDAC3/KDM3A/TET2/TET3 or downregulate DNMT1, thereby affecting ncRNA transcription via chromatin modification

Back to article page