Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jul 6;22(14):7261.
doi: 10.3390/ijms22147261.

The Hypoxia-Long Noncoding RNA Interaction in Solid Cancers

Seung Wan Son  1 , Ba Da Yun  1 , Mun Gyu Song  1 , Jin Kyeong Lee  1 , Soo Young Choi  1 , Hyo Jeong Kuh  2 , Jong Kook Park  1
Affiliations
Review

The Hypoxia-Long Noncoding RNA Interaction in Solid Cancers

Seung Wan Son et al. Int J Mol Sci. .

Abstract

Hypoxia is one of the representative microenvironment features in cancer and is considered to be associated with the dismal prognosis of patients. Hypoxia-driven cellular pathways are largely regulated by hypoxia-inducible factors (HIFs) and notably exert influence on the hallmarks of cancer, such as stemness, angiogenesis, invasion, metastasis, and the resistance towards apoptotic cell death and therapeutic resistance; therefore, hypoxia has been considered as a potential hurdle for cancer therapy. Growing evidence has demonstrated that long noncoding RNAs (lncRNAs) are dysregulated in cancer and take part in gene regulatory networks owing to their various modes of action through interacting with proteins and microRNAs. In this review, we focus attention on the relationship between hypoxia/HIFs and lncRNAs, in company with the possibility of lncRNAs as candidate molecules for controlling cancer.

Keywords: HIF; cancer; hypoxia; hypoxia-inducible factors; long noncoding RNA.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
LncRNAs regulated by hypoxia and HIFs. Both oncogenic (red) and tumor-suppressive (blue) lncRNAs are presented in rounded rectangles. Round brackets denote proteins and miRNAs (orange) that directly interact with lncRNAs and then downstream cellular factors (black) consequently affected by lncRNA-protein/miRNA interactions. Positive regulation is shown by an arrow. An inhibitory effect is designated by a perpendicular line.
Figure 2
Figure 2
LncRNAs modulating the level of HIF-1α. Rounded rectangles represent lncRNAs (red). Rounded brackets denote cellular factors (proteins and miRNAs) involved in lncRNA-mediated HIF-1α regulation. Positive regulation is shown by an arrow.
Figure 3
Figure 3
The regulatory loop between lncRNAs and hypoxia/HIFs. Red rounded rectangles present oncogenic lncRNAs. Tumor-suppressive lncRNAs are shown in blue rounded rectangles. At least through HIF-1α or HIF-2α (displayed in parentheses), hypoxia can modulate the levels of lncRNAs, which in turn affect the expression and activity of HIF-α. The absence of parentheses next to hypoxia suggests the regulation of lncRNAs, possibly in HIF-dependent and/or -independent manners under hypoxia, and that further studies are necessary. Positive regulation is shown by an arrow. An inhibitory effect is designated by a perpendicular line.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Tirpe A.A., Gulei D., Ciortea S.M., Crivii C., Berindan-Neagoe I. Hypoxia: Overview on hypoxia-mediated mechanisms with a focus on the role of hif genes. Int. J. Mol. Sci. 2019;20:6140. doi: 10.3390/ijms20246140. - DOI - PMC - PubMed
    1. Sorensen B.S., Horsman M.R. Tumor hypoxia: Impact on radiation therapy and molecular pathways. Front. Oncol. 2020;10:562. doi: 10.3389/fonc.2020.00562. - DOI - PMC - PubMed
    1. Xue X., Jungles K., Onder G., Samhoun J., Gyorffy B., Hardiman K.M. Hif-3alpha1 promotes colorectal tumor cell growth by activation of jak-stat3 signaling. Oncotarget. 2016;7:11567–11579. doi: 10.18632/oncotarget.7272. - DOI - PMC - PubMed
    1. Mizukami Y., Kohgo Y., Chung D.C. Hypoxia inducible factor-1 independent pathways in tumor angiogenesis. Clin. Cancer Res. 2007;13:5670–5674. doi: 10.1158/1078-0432.CCR-07-0111. - DOI - PubMed
    1. Arsham A.M., Howell J.J., Simon M.C. A novel hypoxia-inducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets. J. Biol. Chem. 2003;278:29655–29660. doi: 10.1074/jbc.M212770200. - DOI - PubMed

LinkOut - more resources