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Int. J. Mol. Sci. 2017, 18(6), 1191; doi:10.3390/ijms18061191

Cross-Kingdom Regulation of Putative miRNAs Derived from Happy Tree in Cancer Pathway: A Systems Biology Approach

Gujarat Institute of Bioinformatics, Gujarat State Biotechnology Mission, Department of Science & Technology, Government of Gujarat, Gandhinagar 382011, India
These authors contributed equally to this work.
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Author to whom correspondence should be addressed.
Academic Editor: Y-h. Taguchi
Received: 20 April 2017 / Revised: 17 May 2017 / Accepted: 27 May 2017 / Published: 3 June 2017
(This article belongs to the Special Issue microRNA Regulation 2017)
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Abstract

MicroRNAs (miRNAs) are well-known key regulators of gene expression primarily at the post-transcriptional level. Plant-derived miRNAs may pass through the gastrointestinal tract, entering into the body fluid and regulate the expression of endogenous mRNAs. Camptotheca acuminata, a highly important medicinal plant known for its anti-cancer potential was selected to investigate cross-kingdom regulatory mechanism and involvement of miRNAs derived from this plant in cancer-associated pathways through in silico systems biology approach. In this study, total 33 highly stable putative novel miRNAs were predicted from the publically available 53,294 ESTs of C. acuminata, out of which 14 miRNAs were found to be regulating 152 target genes in human. Functional enrichment, gene-disease associations and network analysis of these target genes were carried out and the results revealed their association with prominent types of cancers like breast cancer, leukemia and lung cancer. Pathways like focal adhesion, regulation of lipolysis in adipocytes and mTOR signaling pathways were found significantly associated with the target genes. The regulatory network analysis showed the association of some important hub proteins like GSK3B, NUMB, PEG3, ITGA2 and DLG2 with cancer-associated pathways. Based on the analysis results, it can be suggested that the ingestion of the C. acuminata miRNAs may have a functional impact on tumorigenesis in a cross-kingdom way and may affect the physiological condition at genetic level. Thus, the predicted miRNAs seem to hold potentially significant role in cancer pathway regulation and therefore, may be further validated using in vivo experiments for a better insight into their mechanism of epigenetic action of miRNA. View Full-Text
Keywords: miRNA; Camptotheca acuminata; cancer; cross-kingdom regulation; protein-protein interaction network miRNA; Camptotheca acuminata; cancer; cross-kingdom regulation; protein-protein interaction network
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Kumar, D.; Kumar, S.; Ayachit, G.; Bhairappanavar, S.B.; Ansari, A.; Sharma, P.; Soni, S.; Das, J. Cross-Kingdom Regulation of Putative miRNAs Derived from Happy Tree in Cancer Pathway: A Systems Biology Approach. Int. J. Mol. Sci. 2017, 18, 1191.

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