Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation

Abstract

Hypoxia is the major influence factor in physiological and pathological courses which are mainly mediated by hypoxia-inducible factors (HIFs) in response to low oxygen tensions within solid tumors. Under normoxia, HIF signaling pathway is inhibited due to HIF-α subunits degradation. However, in hypoxic conditions, HIF-α is activated and stabilized, and HIF target genes are successively activated, resulting in a series of tumour-specific activities. The activation of HIFs, including HIF-1α, HIF-2α and HIF-3α, subsequently induce downstream target genes which leads to series of responses, the resulting abnormal processes or metabolites in turn affect HIFs stability. Given its functions in tumors progression, HIFs have been regarded as therapeutic targets for improved treatment efficacy. Epigenetics refers to alterations in gene expression that are stable between cell divisions, and sometimes between generations, but do not involve changes in the underlying DNA sequence of the organism. And with the development of research, epigenetic regulation has been found to play an important role in the development of tumors, which providing accumulating basic or clinical evidences for tumor treatments. Here, given how little has been reported about the overall association between hypoxic tumors and epigenetics, we made a more systematic review from epigenetic perspective in hope of helping others better understand hypoxia or HIF pathway, and providing more established and potential therapeutic strategies in tumors to facilitate epigenetic studies of tumors.