Reciprocal regulations between miRNAs and HIF-1α in human cancers

Hypoxia inducible factor-1α (HIF-1α) is a central molecule involved in mediating cellular processes. Alterations of HIF-1α and hypoxically regulated microRNAs (miRNAs) are correlated with patients' outcome in various cancers, indicating their crucial roles on cancer development. Recently, an increasing number of studies have revealed the intricate regulations between miRNAs and HIF-1α in modulating a wide variety of processes, including proliferation, metastasis, apoptosis, and drug resistance, etc. miRNAs are a class of small noncoding RNAs which function as negative regulators by directly targeting mRNAs. Evidence shows that miRNAs can be regulated by HIF-1α at transcriptional level. In turn, HIF-1α itself can be modulated by many miRNAs whose alterations have been implicated in tumorigenesis, thus forming a reciprocal regulation network. These findings add a new layer of complexity to our understanding of HIF-1α regulatory networks. Here, we will provide a comprehensive overview of the current advances about the bidirectional interactions between HIF-1α and miRNAs in human cancers. Besides, the review will summarize the roles of miRNAs/HIF-1α crosstalk according to various cellular processes. Finally, the potential values of miRNAs/HIF-1α loops in clinical applications are discussed.