The strict regulation of HIF-1 & alpha; by non-coding RNAs: new insight towards proliferation, metastasis, and therapeutic resistance strategies

The hypoxic environment is prominently witnessed in most solid tumors and is associated with the promotion of cell proliferation, epithelial-mesenchymal transition (EMT), angiogenesis, metabolic reprogramming, therapeutic resistance, and metastasis of tumor cells. All the effects are mediated by the expression of a transcription factor hypoxia-inducible factor-1a (HIF-1a). HIF-1a transcriptionally modulates the expression of genes responsible for all the aforementioned functions. The stability of HIF-1a is regulated by many proteins and non-coding RNAs (ncRNAs). In this article, we have critically discussed the crucial role of ncRNAs [such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), Piwi-interacting RNAs (piRNAs), and transfer RNA (tRNA)-derived small RNAs (tsRNAs)] in the regulation of stability and expression of HIF-1a. We have comprehensively discussed the molecular mechanisms and relationship of HIF-1a with each type of ncRNA in either promotion or repression of human cancers and therapeutic resistance. We have also elaborated on ncRNAs that are in clinical examination for the treatment of cancers. Overall, the majority of aspects concerning the relationship between HIF-1a and ncRNAs have been discussed in this article.

Automated summary

The hypoxic environment in solid tumors is closely related to various tumor-promoting processes such as cell proliferation, epithelial-mesenchymal transition (EMT), angiogenesis, metabolic reprogramming, therapeutic resistance, and metastasis. The transcription factor HIF-1a is responsible for mediating these effects by regulating the expression of specific genes. In this article, the role of non-coding RNAs (ncRNAs) in modulating the stability and expression of HIF-1a is critically discussed, along with their potential as targets for cancer treatment.