Tumor Microenvironment and Cellular Stress

Abstract

Hypoxia is a central component of the tumor microenvironment and represents a major source of therapeutic failure in cancer therapy. Recent work has provided a wealth of evidence that noncoding RNAs and, in particular, microRNAs, are signifi cant members of the adaptive response to low oxygen in tumors. All pub- lished studies agree that miR-210 specifi cally is a robust target of hypoxia- inducible factors, and the induction of miR-210 is a consistent characteristic of the hypoxic response in normal and transformed cells. Overexpression of miR-210 is detected in most solid tumors and has been linked to adverse prognosis in patients with soft- tissue sarcoma, breast, head and neck, and pancreatic cancer. A wide variety of miR-210 targets have been identifi ed, pointing to roles in the cell cycle, mitochondrial oxidative metabolism, angiogenesis, DNA damage response, and cell survival. Additional microRNAs seem to be modulated by low oxygen in a more tissue-specifi c fashion, adding another layer of complexity to the vast array of protein- coding genes regulated by hypoxia.