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

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.

Dietary plant miRNAs as an augmented therapy: cross-kingdom gene regulation

“…Besides various in vitro and in vivo studies, two recent in silico analyses also strengthened cross-kingdom gene regulation [39,40]. In these reports, the miRNAs were predicted from the available EST datasets of important medicinal plants happy tree (Camptotheca acuminata) [39] and Curcuma longa [40]. In happy tree, the identified miRNAs were predicted to be targeting the cancer associated genes of human and their regulation of expression.…”

“…The stability of miRNAs is due to unique sequence and high GC content in addition to its methylation [35]. Besides various in vitro and in vivo studies, two recent in silico analyses also strengthened cross-kingdom gene regulation [39,40]. In these reports, the miRNAs were predicted from the available EST datasets of important medicinal plants happy tree (Camptotheca acuminata) [39] and Curcuma longa [40].…”

Host Plant-Derived miRNAs Potentially Modulate the Development of a Cosmopolitan Insect Pest, Plutella xylostella

“…MiRNA-mediated cross-kingdom communication has been first reported in mammalian liver, where rice-derived miR168a alters the physiological status of mice via its regulating of the low-density lipoprotein receptor adapter protein 1 (LDLRAP1) [12]. Plant-derived miRNAs have been closely associated with cancer development [13,14] and viral infection [15,16]. These findings suggest that the miRNAs of plants when ingested may contribute to the physiological changes of animals [17].…”

De novo transcriptome of Gymnema sylvestre identified putative lncRNA and genes regulating terpenoid biosynthesis pathway

“…Micromolecules such as long noncoding RNAs (lncRNAs), miRNA etc. have been identified as key regulatory cascade of the eukaryotic transcriptomes, involved in the regulation of important biological processes in plants 48–50 as well as in cross-kingdom gene regulation 51–53 . The study predicted 8 putative candidate lncRNA sequences using computational screening against database of 45 Plants species.…”