Department of Botany, Bioinformatics and Climate Change Impacts Management, School of Sciences, Gujarat University, Ahmedabad, Gujarat, India.
Xcelris Labs Ltd., Ahmedabad, Gujarat, India.
Microrna. 2022;11(1):45-56. doi: 10.2174/2211536611666220318142031.
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.
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.
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.
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.
自古以来，“槟榔叶”（Piper betle）因其宗教、文化和药用价值而备受推崇。来自 Piper betle 的植物化学物质在各种情况下都有效，包括癌症。然而，迄今为止，尚未发现基因组研究或证据来阐明其治疗特性的调节机制。这是首次对槟榔进行 miRNA 预测的研究，也是槟榔基因组资源的首次代表。根据之前的研究，我们吃的植物中的 miRNAs 可以调节基因表达。与此一致，我们的计算机研究表明，槟榔与人类之间存在跨物种的调控。
本研究展示了从 NGS 衍生的转录序列中预测和计算机验证槟榔 miRNA 的方法。通过跨物种调控，也可以理解为种间 RNA 调控，研究了识别受槟榔 miRNA 调控的人类 mRNA 靶标。对人类靶标的功能注释和疾病关联进行了分析，以了解槟榔 miRNA 在人类健康和疾病中的作用。进一步进行了靶标蛋白-蛋白相互作用和表达研究，以破译它们在癌症发展中的作用。
鉴定出六个属于 miR156、miR164、miR172 和 miR535 家族的槟榔 miRNA，靶向涉及各种代谢和疾病过程的 198 个人类 mRNA。血管生成和细胞表面信号通路是与靶标最相关的基因本体论富集，这两个途径都在疾病机制中发挥关键作用，特别是在癌的情况下。在基因-疾病相互作用分析中，发现 40 个基因与癌症有关。根据蛋白质-蛋白质相互作用，发现 CDK6 基因是细胞周期进程的中央调节剂，作为一个枢纽蛋白，影响 CBFB、SAMD9、MDM4、AXIN2 和 NOTCH2 癌基因的作用。进一步的研究表明，pbe-miRNA164a 可作为调节剂，最大限度地减少急性髓系白血病中的疾病严重程度，与正常细胞相比，CDK6 表达最高。
本研究预测的 pbe-miRNA164a 可作为一种有前途的肿瘤血管生成中 CDK6 基因的抑制剂。pbe-miRNA164a 模拟物的体内验证可能为对抗癌症开辟新的机会，并利用槟榔在医疗保健领域的潜力。
