Players of ‘hypoxia orchestra’ – what is the role of FMISO?

Excerpt

Hypoxia is one of the most important factors for exacerbating malignancy, including brain tumors [1‐3]. Hypoxia induces radioresistance [4], chemoresistance [5], HRE-related gene transcription [6], and hypermethylation of tumor suppressor genes [7], making tumor cells more aggressive. These phenomena interact with one another such that the entire set of mechanisms could be described as ‘Hypoxia Orchestra playing Symphony Malignancy’. Of the above cascades, the correlation between hypoxia and HRE-related gene transcription has been well studied. The key player is HIF as the ‘principal conductor of the Orchestra’. HIF leads and controls HRE-related gene translation in hypoxia. In normoxia, HIFα is very unstable, easily degraded by HIF hydroxylases. When the oxygen partial pressure is significantly low owing to rapid tumor growth or a large amount of oxygen consumption, HIF hydroxylases are inactivated, making HIFα more stable. Stable HIFα makes a conjugate with HIF1β, and that conjugates bind to HRE on the DNA and drives transcription of proteins from downstream genes that impact tumor malignancy, such as cell migration, energy metabolism, angiogenic signaling, transcriptional regulation, growth and apoptosis [6]. Over many years, L Bekaert, J.S. Guillamo and coauthors have contributed a significant body of research concerning glioma. Maintaining their focus on malignancy and the prognosis of glioma, they approached these subjects from the standpoints of treatment strategy [8, 9], gene mutation [10], the methylation of DNA [11], and molecular mechanisms [12]. They also performed imaging studies of glioma [13, 14]. …