LncRNAs in hypoxic microenvironment; insight in their impact in cancer biology

Abstract

Hypoxia may facilitate metastasis and tumor advancement in solid tumors. Intratumoral hypoxia may facilitate tumor aggressiveness by stabilizing hypoxia-inducible factor-1α (HIF-1α). Various transcriptional and epigenetic pathways modulate hypoxia-stimulated gene expression and tumor progression. Noncoding RNAs longer than 200 nt are long noncoding RNAs (lncRNAs). Current lncRNA profiling in several human tumor types revealed that lncRNA expression and deregulation vary by tumor type and may undergo transcriptional, genomic, and epigenetic modifications. LncRNAs controlled by hypoxia have emerged as a prominent focus in hypoxia-regulated biology due to their ability to influence multiple biological procedures associated with tumorigenesis. Hypoxia-regulated lncRNAs may influence tumor development, growth, anti-apoptosis, migration, invasion, angiogenesis, and tumor metabolism. In this light, hypoxia-inducible lncRNAs could interact with protein/protein complex and chromatin/epigenetic factors and another mechanism, thus favoring tumorigenesis. Conversely, lncRNAs may control hypoxia signaling by stabilizing HIF-1α via several mechanisms. Nonetheless, several undiscovered lncRNAs remain that may mediate or regulate the hypoxia axis. Consequently, the novel lncRNAs modulated by hypoxia or that influence hypoxia signaling have yet to be discovered and thoroughly described. Herein, we aim to classify suitable lncRNA targets to offer a feasible therapeutic modality for hypoxia-driven cancers.

Keywords: Cancer; Epigenetics; HIF-1α; Hypoxia; LncRNA.