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Review
. 2021 Oct;44(5):521-533.
doi: 10.1016/j.bj.2021.03.005. Epub 2021 Mar 24.

The role of hypoxia-induced long noncoding RNAs (lncRNAs) in tumorigenesis and metastasis

Pei-Hua Peng  1 , Kai-Wen Hsu  2 , Joseph Chieh-Yu Lai  3 , Kou-Juey Wu  4
Affiliations
Review

The role of hypoxia-induced long noncoding RNAs (lncRNAs) in tumorigenesis and metastasis

Pei-Hua Peng et al. Biomed J. 2021 Oct.

Abstract

Long noncoding RNAs (lncRNAs) are noncoding RNAs with length greater than 200 nt. The biological roles and mechanisms mediated by lncRNAs have been extensively investigated. Hypoxia is a proven microenvironmental factor that promotes solid tumor metastasis. Epithelial-mesenchymal transition (EMT) is one of the major mechanisms induced by hypoxia to contribute to metastasis. Many lncRNAs have been shown to be induced by hypoxia and their roles have been delineated. In this review, we focus on the hypoxia-inducible lncRNAs that interact with protein/protein complex and chromatin/epigenetic factors, and the mechanisms that contribute to metastasis. The role of a recently discovered lncRNA RP11-390F4.3 in hypoxia-induced EMT is discussed. Whole genome approaches to delineating the association between lncRNAs and histone modifications are discussed. Other topics related to hypoxia-induced tumor progression but require further investigation are also mentioned. The clinical significance and treatment strategy targeted against lncRNAs are discussed. The review aims to identify suitable lncRNA targets that may provide feasible therapeutic venues for hypoxia-involved cancers.

Keywords: Epigenetics; Epithelial–mesenchymal transition; Hypoxia; LncRNA RP11-390F4.3; Metastasis; lncRNAs.

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Conflict of interest statement

Conflicts of interest There is no competing interest among the authors.

Figures

Fig. 1
Fig. 1
Summary of hypoxia-induced lncRNAs that interact with protein/protein complex, leading to different outcomes.
Fig. 2
Fig. 2
A model of hypoxia-induced lncRNAs that interact with epigenetic regulators to regulate histone modifications or modulate DNA methylation, leading to changes in gene expression.
Fig. 3
Fig. 3
A model of hypoxia-induced lncRNA RP11-390F4.3 that regulates four “core” EMT transcriptional regulators to mediated hypoxia-induced EMT, metastasis, and tumor progression.
See this image and copyright information in PMC

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