Cross- and intra-kingdom miRNA-mediated transcriptomic regulation by Conocarpus erectus L.: a novel insight into genome stability, epigenetic control, and neurodegenerative pathways

Abstract

Conocarpus erectus L., a traditionally important medicinal plant, is increasingly recognized as a potential source of bioactive small RNAs with therapeutic relevance. Leveraging a cross- and intra-kingdom computational framework, we identified and characterized 30 novel microRNAs (miRNAs) from the C. erectus transcriptome. These plant-derived miRNAs were predicted to target genes in both Homo sapiens and Arabidopsis thaliana, thereby offering a unique opportunity to explore conserved and species-specific molecular mechanisms. Functional enrichment of human and A. thaliana gene targets revealed significant involvement in regulatory networks controlling genome integrity, including pathways related to MAPK signaling, PI3K-Akt, insulin, and neurotrophin signaling, as well as cellular senescence. In humans, top-ranked hub genes such as CDC42, MAPK14, PIK3R1, AR, and NTRK2 were implicated in genome instability-associated conditions, including neurodegeneration and metabolic diseases. In parallel, the A. thaliana targets provided insights into conserved post-transcriptional regulatory networks and stress adaptation pathways. Notably, both organisms demonstrated miRNA influence over genes involved in DNA repair, epigenetic modulation, and signal transduction. Molecular dynamics simulations validated the structural stability of the CDC42–cer-miR1134-5p complex over a 300 ns trajectory, suggesting stable and functional RNA-RNA interactions. Collectively, our findings propose that C. erectus miRNAs act as interspecies epigenetic regulators with the potential to impact genome stability, offering promising leads for novel RNA-based therapeutics in neurodegenerative and genome instability-linked diseases.

Keywords

MicroRNA / C. erectus L. / Functional enrichment / Network analysis / Diabetes / Cross-kingdom regulation / Intra-kingdom analysis / Computational genomics / miRNA–mRNA complex MD simulation

Highlight

•	Discovery of novel cross-kingdom miRNAs from Conocarpus erectus L. A total of 30 novel miRNAs were identified from the transcriptome of C. erectus, with predicted regulatory roles in both Homo sapiens and Arabidopsis thaliana, highlighting their dual inter- and intra-kingdom significance.
•	Regulation of genome stability and disease-associated pathways. Functional analysis of human gene targets revealed enrichment in key pathways related to genome maintenance, including MAPK, PI3K-Akt, insulin signaling, and neurotrophin signaling—mechanistically linked to DNA repair and neuronal health.
•	Key genome regulatory hub genes identified. Network topology pinpointed CDC42, MAPK14, PIK3R1, NTRK2, and AR as central regulatory nodes potentially modulated by C. erectus miRNAs, each implicated in genome instability, diabetes, and neurodegenerative disorders.
•	Comparative analysis with A. thaliana validates conserved molecular mechanisms. Target prediction in Arabidopsis thaliana confirmed conserved stress-responsive and transcriptional regulatory networks, supporting the evolutionary conservation of plant miRNA functions.
•	Molecular dynamics confirms mirna–mrna complex stability. A 300 ns molecular dynamics simulation demonstrated stable and sustained binding between cer-miR1134-5p and the CDC42 transcript, reinforcing the potential for functional post-transcriptional regulation.

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Shenzhen University School of Medicine; Fondazione Istituto FIRC di Oncologia Molecolare

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