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Review
. 2020 Feb 3;39(1):27.
doi: 10.1186/s13046-020-1535-y.

The interplay between HIF-1α and noncoding RNAs in cancer (VSports手机版)

Affiliations
Review

The interplay between HIF-1α and noncoding RNAs in cancer

Xiafeng Peng et al. J Exp Clin Cancer Res. .

Erratum in

Abstract

Hypoxia is a classic characteristic of the tumor microenvironment with a significant impact on cancer progression and therapeutic response. Hypoxia-inducible factor-1 alpha (HIF-1α), the most important transcriptional regulator in the response to hypoxia, has been demonstrated to significantly modulate hypoxic gene expression and signaling transduction networks. In past few decades, growing numbers of studies have revealed the importance of noncoding RNAs (ncRNAs) in hypoxic tumor regions. These hypoxia-responsive ncRNAs (HRNs) play pivotal roles in regulating hypoxic gene expression at the transcriptional, posttranscriptional, translational and posttranslational levels VSports手机版. In addition, as a significant gene expression regulator, ncRNAs exhibit promising roles in regulating HIF-1α expression at multiple levels. In this review, we briefly elucidate the reciprocal regulation between HIF-1α and ncRNAs, as well as their effect on cancer cell behaviors. We also try to summarize the complex feedback loop existing between these two components. Moreover, we evaluated the biomarker potential of HRNs for the diagnosis and prognosis of cancer, as well as the potential clinical utility of shared regulatory mechanisms between HIF-1α and ncRNAs in cancer treatment, providing novel insights into tumorigenicity, which may lead to innovative clinical applications. .

Keywords: HIF-1α; carcinogenesis; clinical practice; ncRNA. V体育安卓版.

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Conflict of interest statement

The authors declare that they have no competing interests.

"VSports最新版本" Figures

Fig. 1
Fig. 1
HIF-1α transcriptionally activates target genes in response to hypoxia. Under normoxia, HIF-1α is subjected to hydroxylation by PHDs and other prolyl hydroxylases. Hydroxylated HIF-1α is recognized by VHL proteins that target HIF-1α for subsequent ubiquitination and proteasomal degradation. In addition to regulation of the degradation of HIF-1α, the transcriptional activity of HIF-1α is regulated FIH1, which hydroxylates an asparagine residue of HIF-1α in its C-terminal transactivation domain and therefore blocks the interaction between HIF-1α and CBP/p300. During hypoxia, the hydroxylation reactions are diminished, resulting in HIF-1α accumulation and enhanced transcriptional activity, dimerization with HIF-1β, binding to target genes and activation of target genes through recruitment of CBP/p300 and formation of the transcription initiation complex.
Fig. 2
Fig. 2
Reciprocal feedback loops between HIF-1α and ncRNAs. In addition to a unidirectional regulation pattern, there are several direct or indirect feedback loops between HIF-1α and ncRNAs. It seems quite feasible that the ncRNAs, HIF-1α and other co-operators would eventually intertwine to form mutually reciprocal feedback loops in both positive and negative manners. In addition to common feedback loops, lincRNA-p21 and HISLA can block VHL- and PHD-dependent HIF-1α repression instead of directly interacting with HIF-1α and other co-operators.

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