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. 2017 Jun 3;18(6):1191.
doi: 10.3390/ijms18061191.

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

Dinesh Kumar  1 , Swapnil Kumar  2 , Garima Ayachit  3 , Shivarudrappa B Bhairappanavar  4 , Afzal Ansari  5 , Priyanka Sharma  6 , Subhash Soni  7 , Jayashankar Das  8
Affiliations

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

Dinesh Kumar et al. Int J Mol Sci. .

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.

Keywords: Camptotheca acuminata; cancer; cross-kingdom regulation; miRNA; protein-protein interaction network.

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Conflict of interest statement

Authors declare no conflicts of interests.

Figures

Figure 1
Figure 1
Predicted hairpin stem loop secondary structures of 14 putative miRNAs identified in C. acuminate. (a) cac-miR-3440-3p; (b) cac-miR-5653; (c) cac-miR-156e-3p; (d) cac-miR5049-3p; (e) cac-miR-5780d; (f) cac-miR-4723-3p; (g) cac-miR-7398f-5p; (h) cac-miR-548d-3p; (i) cac-miR-6903-5p; (j) cac-miR-7009-3p; (k) cac-miR-5291c; (l) cac-miR-5532; (m) cac-miR-29c-5p; (n) cac-miR-8157-3p; Mature sequences are marked with red color and the actual size of the precursors may be slightly longer than the one shown in the figure.
Figure 2
Figure 2
Gene-disease associations (with seven prominent cancer types).
Figure 3
Figure 3
(a) Top 10 Hub nodes detected by Degree method, Top 10 hub nodes are marked with red color, which have been detected based on degree method; (b) Top 10 Hub nodes detected by Bottleneck method, Top 10 hub nodes are marked with red color, which have been detected based on bottleneck method.
Figure 3
Figure 3
(a) Top 10 Hub nodes detected by Degree method, Top 10 hub nodes are marked with red color, which have been detected based on degree method; (b) Top 10 Hub nodes detected by Bottleneck method, Top 10 hub nodes are marked with red color, which have been detected based on bottleneck method.
Figure 4
Figure 4
Brief workflow of the study.
See this image and copyright information in PMC

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