Identification of Key Hub Genes and Their Role in Regulating IPP Biosynthesis Pathways in Ethylene-Stimulated Hevea brasiliensis Seedlings: A Bioinformatic Study

The Pará rubber tree (Hevea brasiliensis) is the primary commercial source of natural rubber. Latex production in this species can be significantly enhanced by ethylene stimulation, typically applied as ethephon. However, the molecular mechanisms underlying this response remain to be fully elucidated. In this study, changes in gene expression in rubber tree seedlings exposed to ethephon were investigated using bioinformatic approaches. For this purpose, microarray data (GSE174832) from the NCBI Gene Expression Omnibus were analyzed using GEO2R. Differentially expressed genes (DEGs) were identified at 24 and 48 hours post-ethephon treatment compared with controls, and DEGs shared between the two time points were selected for further analysis. Specifically, the mevalonate (MVA) and methylerythritol-4-phosphate (MEP) pathways, which provide isopentenyl diphosphate (IPP) for isoprenoid biosynthesis, together with downstream isoprenoid- and rubber-related genes, were examined. A protein-protein interaction (PPI) network was constructed to identify hub genes governing these responses. Seven genes—DXS, ISPE, HMGS, HMG1, FPS2, SQE1, and SQE3—were consistently identified as hub genes by MCC, EPC, and MCODE. Six hub genes were down-regulated at both time points, whereas ISPE was up-regulated. Functional enrichment prominently highlighted terpenoid backbone biosynthesis. FPS2 and CPT1 were down-regulated, whereas GGPPS1 was up-regulated, indicating a non-uniform transcriptional response among isoprenoid-related genes. Overall, the results do not support broad transcriptional activation of the rubber biosynthetic machinery in ethephon-treated seedling stems but identify persistent ethephon-responsive genes associated with isoprenoid metabolism. These genes represent candidates for further investigation and experimental validation in laticifer tissues.