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Review
. 2020 Nov 23;21(22):8855.
doi: 10.3390/ijms21228855.

LncRNAs in Ovarian Cancer Progression, Metastasis, and Main Pathways: ceRNA and Alternative Mechanisms

Eleonora A Braga  1   2 , Marina V Fridman  3 , Alexey A Moscovtsev  1 , Elena A Filippova  1 , Alexey A Dmitriev  4 , Nikolay E Kushlinskii  5
Affiliations
Review

LncRNAs in Ovarian Cancer Progression, Metastasis, and Main Pathways: ceRNA and Alternative Mechanisms

Eleonora A Braga et al. Int J Mol Sci. .

Abstract

Ovarian cancer (OvCa) develops asymptomatically until it reaches the advanced stages with metastasis, chemoresistance, and poor prognosis. Our review focuses on the analysis of regulatory long non-coding RNAs (lncRNAs) competing with protein-coding mRNAs for binding to miRNAs according to the model of competitive endogenous RNA (ceRNA) in OvCa. Analysis of publications showed that most lncRNAs acting as ceRNAs participate in OvCa progression: migration, invasion, epithelial-mesenchymal transition (EMT), and metastasis. More than 30 lncRNAs turned out to be predictors of survival and/or response to therapy in patients with OvCa. For a number of oncogenic (CCAT1, HOTAIR, NEAT1, and TUG1 among others) and some suppressive lncRNAs, several lncRNA/miRNA/mRNA axes were identified, which revealed various functions for each of them. Our review also considers examples of alternative mechanisms of actions for lncRNAs besides being ceRNAs, including binding directly to mRNA or protein, and some of them (DANCR, GAS5, MALAT1, and UCA1 among others) act by both mechanisms depending on the target protein. A systematic analysis based on the data from literature and Panther or KEGG (Kyoto Encyclopedia of Genes and Genomes) databases showed that a significant part of lncRNAs affects the key pathways involved in OvCa metastasis, EMT, and chemoresistance.

Keywords: competitive endogenous RNAs; long non-coding RNAs; metastasis; miRNAs; oncogenic and suppressive lncRNAs; ovarian cancer; signaling pathways.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Signaling pathways involved in ovarian cancer pathogenesis. Straight arrows indicate activation of gene (protein) expression and blunt arrows indicate inhibition of gene (protein) expression. Two consecutive arrows mean that there may be other participants in the process, i.e. the connection is not direct, but through intermediaries.
Figure 2
Figure 2
Signaling pathways involved in epithelial-mesenchymal transition (EMT) in ovarian cancer. Straight arrows indicate activation of gene (protein) or process and blunt arrows indicate inhibition of gene (protein) or process.
Figure 3
Figure 3
Two axes, regulated by lncRNA GAS5 (growth arrest-specific 5), both with suppressive functions (left), and two lncRNA MEG3 (maternally expressed 3) axes with oncogenic and suppressive functions (right). Blunt arrows indicate inhibition of miRNA or gene (protein) expression and straight double arrows indicate manifestation by a given gene of suppressive or oncogenic properties.
Figure 4
Figure 4
Set of multiple axes regulated by the oncogenic lncRNA CCAT1 (colon cancer-associated transcript 1) in ovarian cancer. Blunt arrows indicate inhibition of miRNA or gene (protein) expression.
Figure 5
Figure 5
Set of multiple axes regulated by the oncogenic lncRNA HOTAIR (HOX transcript antisense intergenic RNA) in ovarian cancer. Blunt arrows indicate inhibition of miRNA or gene (protein) expression.
Figure 6
Figure 6
Set of multiple axes, regulated by the oncogenic lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) in ovarian cancer. Blunt arrows indicate inhibition of miRNA or gene (protein) expression.
Figure 7
Figure 7
Set of multiple axes regulated by the oncogenic lncRNA NEAT1 (nuclear-enriched abundant transcript 1). RNA-binding proteins (RBP) Hur (Hu antigen R) and LIN28B (Lin-28 homolog B), stabilizing NEAT1, are also shown. Blunt arrows indicate inhibition of miRNA or gene (protein) expression and straight arrows indicate stabilizing and activating effect of RBP Hur and LIN28B.
See this image and copyright information in PMC

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