Hypoxia-induced tumor malignancy and drug resistance: Role of microRNAs

Abstract

Hypoxia is an intricate microenvironment associated with aggressiveness and chemoresistance of a variety of solid tumors. Hypoxia-inducible factors (HIFs) regulate downstream target genes that render cancer cells capacity to adapt to the hostile, low-oxygen stress for survival. HIF has been estimated to regulate more than 5% of total human genes. The HIF-regulated gene network has been shown to be associated with resistance to chemotherapy, metastasis, tumor recurrence, and reduced overall survival rate. With the increasing findings that microRNAs (miRNAs) are aberrantly expressed under hypoxia, which participate positively or negatively in regulating hypoxia-related genes, the signaling pathway of hypoxia becomes more and more complicated. Based on the roles of miRNAs in tumor development and drug resistance, the potential of targeting miRNAs as a therapeutic regimen has been emphasized recently. Therefore, understanding the regulation and functions of miRNAs in cancer cells will provide us with useful information for designing more efficacious treatment regimens. In this article, we will review the biological kinship of hypoxia and hypoxia-regulated miRNAs in cancer malignancy and drug resistance.