MiRNA therapeutics based on logic circuits of biological pathways

Abstract

BackgroundIn silico experiments, with the aid of computer simulation, speed up the process of in vitro or in vivo experiments. Cancer therapy design is often based on signalling pathway. MicroRNAs (miRNA) are small non-coding RNA molecules. In several kinds of diseases, including cancer, hepatitis and cardiovascular diseases, they are often deregulated, acting as oncogenes or tumor suppressors. miRNA therapeutics is based on two main kinds of molecules injection: miRNA mimics, which consists of injection of molecules that mimic the targeted miRNA, and antagomiR, which consists of injection of molecules inhibiting the targeted miRNA. Nowadays, the research is focused on miRNA therapeutics. This paper addresses cancer related signalling pathways to investigate miRNA therapeutics.ResultsIn order to prove our approach, we present two different case studies: non-small cell lung cancer and melanoma. KEGG signalling pathways are modelled by a digital circuit. A logic value of 1 is linked to the expression of the corresponding gene. A logic value of 0 is linked to the absence (not expressed) gene. All possible relationships provided by a signalling pathway are modelled by logic gates. Mutations, derived according to the literature, are introduced and modelled as well. The modelling approach and analysis are widely discussed within the paper. MiRNA therapeutics is investigated by the digital circuit analysis. The most effective miRNA and combination of miRNAs, in terms of reduction of pathogenic conditions, are obtained. A discussion of obtained results in comparison with literature data is provided. Results are confirmed by existing data.ConclusionsThe proposed study is based on drug discovery and miRNA therapeutics and uses a digital circuit simulation of a cancer pathway. Using this simulation, the most effective combination of drugs and miRNAs for mutated cancer therapy design are obtained and these results were validated by the literature. The proposed modelling and analysis approach can be applied to each human disease, starting from the corresponding signalling pathway.

Implementation of novel boolean logic gates for IMPLICATION and XOR functions using riboregulators

“…Concerning disease treatment, microRNA and long non-coding RNA play crucial roles in various diseases, including cardiovascular diseases, hepatitis, diabetes mellitus, cancer, etc [ 28–32 ]. If miRNAs are used as inputs to these logic gates, it may provide an alternative way of thinking about disease diagnosis and treatment [ 33 , 34 ]. If these ideas become reality, biological logic gates could be used to accomplish special tasks in many aspects of lives of people.…”

MicroRNAs and Sepsis-Induced Cardiac Dysfunction: A Systematic Review

“…In the last few years, interest in how miRNAs influence various signaling pathways has increased [ 13 , 78 , 79 , 80 ]. In particular, their role in the pathophysiology of diseases has been the subject of many studies [ 15 , 81 , 82 , 83 , 84 ].…”

Tumor Immune Microenvironment and Its Related miRNAs in Tumor Progression

“…The development of miRNA as a clinical drug is undoubtedly imminent. Currently, it is believed that there are two main strategies for developing miRNA as therapeutics ( 120 ). Firstly, for miRNAs with cancer-inhibiting effects, miRNA analogs can be delivered through the system to promote their long-lasting and efficient anticancer effects ( 121 ).…”