MicroRNA target identification: lessons from hypoxamiRs.

Significance: MicroRNAs (miRNAs) are small noncoding RNAs that have emerged as key regulators of many physiological and pathological processes, including those relevant to hypoxia such as cancer, neurological dysfunctions, myocardial infarction, and lung diseases.

Recent Advances: During the last 5 years, miRNAs have been shown to play a role in the regulation of the cellular response to hypoxia. The identification of several bona fide targets of these hypoxamiRs has underlined their pleiotropic functions and the complexity of the molecular rules directing miRNA::target transcript pairing.

Critical Issues: This review outlines the main in silico and experimental approaches used to identify the targetome of hypoxamiRs and presents new recent relevant methodologies for future studies.

Future Directions: Since hypoxia plays key roles in many pathophysiological conditions, the precise characterization of regulatory hypoxamiRs networks will be instrumental both at a fundamental level and for their future potential therapeutic applications.