Emerging roles of miR-210 and other non-coding RNAs in the hypoxic response.

Hypoxia is a key component of the tumor microenvironment and represents a well-documented source of therapeutic failure in clinical oncology. Recent work has provided support for the idea that non-coding RNAs, and in particular, microRNAs, may play important roles in the adaptive response to low oxygen in tumors. Specifically, all published studies agree that the induction of microRNA-210 (miR-210) is a consistent feature of the hypoxic response in both normal and malignant cells. miR-210 is a robust target of hypoxia-inducible factors, and its overexpression has been detected in a variety of diseases with a hypoxic component, including most solid tumors. High levels of miR-210 have been linked to an in vivo hypoxic signature and to adverse prognosis in breast and pancreatic cancer patients. A wide variety of miR-210 targets have been identified, pointing to roles in mitochondrial metabolism, angiogenesis, DNA damage response, apoptosis, and cell survival. Such targets are suspected to affect the development of tumors in multiple ways; therefore, an increased knowledge about miR-210's functions may lead to novel diagnostic and therapeutic approaches in cancer.