Motwani Harsha, Patel Maulikkumar, Nanavaty Vishal, Dixit Nandan, Rawal Rakesh M, Patel Saumya K, Solanki Hitesh A
Department of Botany, Bioinformatics and Climate Change Impacts Management, Gujarat University, Ahmedabad-380009, Gujarat, India.
Department of Life Science, School of Sciences, Gujarat University, Ahmedabad-380009, Gujarat, India.
Funct Integr Genomics. 2023 Feb 2;23(1):55. doi: 10.1007/s10142-023-00976-7.
Cross-species post-transcriptional regulatory potential of plant derived small non-coding microRNAs (miRNAs) has been well documented by plenteous studies. MicroRNAs are transferred to host cells via oral ingestion wherein they play a decisive role in regulation of host genes; thus, miRNAs have evolved as the nascent bioactive molecules imparting pharmacological values to traditionally used medicinal plants. The present study aims to investigate small RNA profiling in order to uncover the potential regulatory role of miRNAs derived from Andrographis paniculata, one of the most widely used herb by tribal communities for liver disorders and document the pharmacological properties of A. paniculata miRNAs. In this study, high-throughput sequencing method was used to generate raw data, ~ 60 million sequences were generated from A. paniculata leaves. Using computational tools and bioinformatics approach, analyses of 3,480,097 clean reads resulted in identification of 3440 known and 51 putative novel miRNAs regulating 1365 and 192 human genes respectively. Remarkably, the identified plausible novel miRNAs apa-miR-5, apa-miR-1, apa-miR-26, and apa-miR-30 are projected to target significant host genes including CDK6, IKBKB, TRAF3, CHD4, MECP2, and ADIPOQ. Subsequent annotations revealed probable involvement of the target genes in various pathways for instance p38-MAPK, AKT, AMPK, NF-Kβ, ERK, WNT signalling, MYD88 dependant cascade, and pathways in cancer. Various diseases such as human papilloma virus infection, Alzheimer's, Non-alcoholic Fatty Liver, Alcoholic liver diseases, HepatoCellular Carcinoma (HCC), and numerous other cancers were predominantly found to be linked with target genes. Our findings postulate novel interpretations regarding modulation of human transcripts by A. paniculata miRNAs and exhibit the regulation of human diseases by plant-derived miRNAs. Though our study elucidates miRNAs as novel therapeutic agents, however, experimental validations for assessment of therapeutic potential of these miRNAs are still warranted.
大量研究充分证明了植物来源的小非编码微小RNA（miRNA）的跨物种转录后调控潜力。微小RNA通过口服摄入转移到宿主细胞中，在宿主基因调控中起决定性作用；因此，微小RNA已演变为赋予传统药用植物药理价值的新生生物活性分子。本研究旨在通过小RNA谱分析，揭示穿心莲（部落社区最广泛用于治疗肝脏疾病的草药之一）来源的微小RNA的潜在调控作用，并记录穿心莲微小RNA的药理特性。在本研究中，采用高通量测序方法生成原始数据，从穿心莲叶片中生成了约6000万个序列。使用计算工具和生物信息学方法，对3480097条clean reads进行分析，分别鉴定出3440个已知的和51个推定的新型微小RNA，它们分别调控1365个和192个人类基因。值得注意的是，鉴定出的看似合理的新型微小RNA apa-miR-5、apa-miR-1、apa-miR-26和apa-miR-30预计靶向重要的宿主基因，包括CDK6、IKBKB、TRAF3、CHD4、MECP2和ADIPOQ。随后的注释揭示了靶基因可能参与各种途径，例如p38-MAPK、AKT、AMPK、NF-Kβ、ERK、WNT信号传导、MYD88依赖性级联反应以及癌症相关途径。各种疾病，如人乳头瘤病毒感染、阿尔茨海默病、非酒精性脂肪肝、酒精性肝病、肝细胞癌（HCC）和许多其他癌症，主要被发现与靶基因有关。我们的研究结果对穿心莲微小RNA对人类转录本的调控提出了新的解释，并展示了植物来源的微小RNA对人类疾病的调控作用。尽管我们的研究将微小RNA阐明为新型治疗剂，但对这些微小RNA治疗潜力评估的实验验证仍然是必要的。
