Dynamical Analysis of a Boolean Network Model of the Oncogene Role of lncRNA ANRIL and lncRNA UFC1 in Non-Small Cell Lung Cancer
Departamento de Ciência da Computação, Instituto de Matemática e Estatística, Universidade de São Paulo, Rua do Matão 1010, São Paulo 05508-090, SP, Brazil
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Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Academic Editors: Prakash Kulkarni and Mohit Kumar Jolly
Biomolecules 2022, 12(3), 420; https://doi.org/10.3390/biom12030420
Received: 14 February 2022
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Revised: 1 March 2022
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Accepted: 1 March 2022
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Published: 9 March 2022
(This article belongs to the Special Issue Cancer Systems Biology: Investigating Cancer Dynamics from a Complex Systems Perspective)
Long non-coding RNA (lncRNA) such as ANRIL and UFC1 have been verified as oncogenic genes in non-small cell lung cancer (NSCLC). It is well known that the tumor suppressor microRNA-34a (miR-34a) is downregulated in NSCLC. Furthermore, miR-34a induces senescence and apoptosis in breast, glioma, cervical cancer including NSCLC by targeting Myc. Recent evidence suggests that these two lncRNAs act as a miR-34a sponge in corresponding cancers. However, the biological functions between these two non-coding RNAs (ncRNAs) have not yet been studied in NSCLC. Therefore, we present a Boolean model to analyze the gene regulation between these two ncRNAs in NSCLC. We compared our model to several experimental studies involving gain- or loss-of-function genes in NSCLC cells and achieved an excellent agreement. Additionally, we predict three positive circuits involving miR-34a/E2F1/ANRIL, miR-34a/E2F1/UFC1, and miR-34a/Myc/ANRIL. Our circuit- perturbation analysis shows that these circuits are important for regulating cell-fate decisions such as senescence and apoptosis. Thus, our Boolean network permits an explicit cell-fate mechanism associated with NSCLC. Therefore, our results support that ANRIL and/or UFC1 is an attractive target for drug development in tumor growth and aggressive proliferation of NSCLC, and that a valuable outcome can be achieved through the miRNA-34a/Myc pathway.
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Keywords:
Long non-coding RNA; ANRIL; UFC1; miRNA-34a; Myc; Boolean model; feedback loops; senescence; apoptosis; NSCLC
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MDPI and ACS Style
Gupta, S.; Hashimoto, R.F. Dynamical Analysis of a Boolean Network Model of the Oncogene Role of lncRNA ANRIL and lncRNA UFC1 in Non-Small Cell Lung Cancer. Biomolecules 2022, 12, 420. https://doi.org/10.3390/biom12030420
AMA Style
Gupta S, Hashimoto RF. Dynamical Analysis of a Boolean Network Model of the Oncogene Role of lncRNA ANRIL and lncRNA UFC1 in Non-Small Cell Lung Cancer. Biomolecules. 2022; 12(3):420. https://doi.org/10.3390/biom12030420
Chicago/Turabian StyleGupta, Shantanu, and Ronaldo F. Hashimoto. 2022. "Dynamical Analysis of a Boolean Network Model of the Oncogene Role of lncRNA ANRIL and lncRNA UFC1 in Non-Small Cell Lung Cancer" Biomolecules 12, no. 3: 420. https://doi.org/10.3390/biom12030420
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