Title:Understanding the Molecular Mechanisms of Betel miRNAs on Human
Health
Volume: 11
Issue: 1
Author(s): Toral Manvar, Naman Mangukia, Saumya Patel and Rakesh Rawal*
Affiliation:
- Department of Life Sciences, School of Sciences, Gujarat University, Ahmedabad, Gujarat, India
Keywords:
Piper betle, miRNAs, eukaryotic cross kingdom interaction, gene-disease association, functional analysis, cancer, protein-protein interaction network, gene expression.
Abstract:
Background: Since ancient times, "betel leaf" (Piper betle) has been revered for its religious,
cultural, and medicinal properties. Phytochemicals from the Piper betle are effective in a variety
of conditions, including cancer. To date, however, no genomic study or evidence has been found to
elucidate the regulatory mechanism that underpins its therapeutic properties. This is the first study of
its kind to predict Piper betle miRNAs and also the first genomics source representation of Piper betle.
According to previous research, miRNAs from the plants we eat can regulate gene expression. In line
with this, our in-silico study revealed that Piper betle and human cross-kingdom control occurs.
Methods: This study demonstrates the prediction and in-silico validation of Piper betle miRNAs from
NGS-derived transcript sequences. The cross-kingdom regulation, which can also be understood as inter-
species RNA regulation, was studied to identify human mRNA targets controlled by Piper betle
miRNAs. Functional annotation and gene-disease association of human targets were performed to understand
the role of Piper betle miRNAs in human health and disease. The protein-protein interaction
and expression study of targets was further carried out to decipher their role in cancer development.
Results: Identified six Piper betle miRNAs belonging to miR156, miR164, miR172, and miR535 families
were discovered to target 198 human mRNAs involved in various metabolic and disease processes.
Angiogenesis and the cell surface signaling pathway were the most enriched gene ontology correlated
with targets, both of which play a critical role in disease mechanisms, especially in the case of carcinoma.
In an analysis of gene-disease interactions, 40 genes were found to be related to cancer. According
to a protein-protein interaction, the CDK6 gene, which is thought to be a central regulator of cell
cycle progression, was found as a hub protein, affecting the roles of CBFB, SAMD9, MDM4, AXIN2,
and NOTCH2 oncogenes. Further investigation revealed that pbe-miRNA164a can be used as a regulator
to minimise disease severity in Acute Myeloid Leukemia, where CDK6 expression is highest compared
to normal cells.
Conclusion: The predicted pbe-miRNA164a in this study can be a promising suppressor of CDK6
gene involved in tumour angiogenesis. In vivo validation of the pbe-miRNA164a mimic could pave the
way for new opportunities to fight cancer and leverage the potential of Piper betle in the healthcare
sector.
