Abstract
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.
Highlights
IntroductionLong non-coding RNAs (LncRNAs) participate in multiple biological processes such as cell-cycle progression, apoptosis and genome stability [1]
Our results support that ANRIL and/or UFC1 is an attractive target for drug development in tumor growth and aggressive proliferation of non-small cell lung cancer (NSCLC), and that a valuable outcome can be achieved through the miRNA-34a/Myc pathway
Using the biochemical information mentioned above, we propose a Boolean model for the G1/S checkpoint in NSCLC cells considering the effect of miR-34a by Long non-coding RNA (lncRNA) such as ANRIL and UFC1 in NSCLC
Summary
LncRNAs participate in multiple biological processes such as cell-cycle progression, apoptosis and genome stability [1]. In this context, a study of Nie et al [2] explored the role of the lncRNA antisense noncoding RNA gene at the INK4 locus (hereafter referred to as ANRIL) in NSCLC progression. The study further demonstrated that the overexpression of ANRIL reduces p21 and KLF2 by inducing EZH2 and modulates proliferation in NSCLC while the knockdown of ANRIL regulates apoptosis and cell-cycle arrest by halting the NSCLC progression. Zang et al [3] found that the long intergenic noncoding RNA UFC1 (hereafter referred to as UFC1) expression level was increased in the tumor tissues and serum of NSCLC patients [3]
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