Menglan Wang | Search PubMed

PubMed2025

Genomic mechanism of aroma terpenoids biosynthesis in plants.

BACKGROUND: Aroma terpenoids are crucial plant secondary metabolites with physiological and commercial importance. Interestingly, both closely and distantly related species can synthesize identical aroma terpenoids. With the development of genome sequencing technology, it has become possible to elucidate the genomic mechanism underlying this phenomenon. AIM: This review highlights whole-genome data as a robust strategy for investigating the genomic mechanism of aroma terpenoids biosynthesis in plants, and provides new perspectives on the origin, evolution, and engineering of terpene synthases (TPSs). This aims to significantly benefit plant breeding and enhance suitability for industrial production. KEY SCIENTIFIC CONCEPTS OF REVIEW: Genomic mechanism of aroma terpenoids biosynthesis in plant genomes is the genetic and evolutionary dynamics. We elaborate the genomic mechanism governing the biosynthesis of plant-derived aroma terpenoids in three dimensions: (1) Genome-wide identification and phylogenetic analyses of TPSs. The same aroma terpenoids were produced by numerous plant species with chromosome-level genomes. Based on 34 plant genomes, we identified 1643 TPSs and classified them into seven subfamilies. (2) Functional and structural basis of TPSs. We found that TPSs with identical functions in distant species exhibit low sequence similarity but conserved active cavity architectures. Conversely, functionally distinct TPSs in closely related species cluster phylogenetically but differ in active cavity structures. (3) Patterns of TPS gene origination. Comparative genomic analyses within and between species revealed three patterns enabling TPSs to acquire the same functions: tandem duplications, dispersed duplications, and genes without duplication.

Terpenes↗

PubMed2025

Redistribution of super-enhancers promotes malignancy in human hepatocellular carcinoma.

INTRODUCTION: Super-enhancers (SEs) are defined as the regulatory region where intensive transcriptional cofactors bind. Dysregulation of SEs is related to multiple diseases, however, its role in hepatocellular carcinoma (HCC) remains elusive. OBJECTIVES: This work aimed to reveal the dysregulation of SEs in HCC and the therapeutic potential for HCC treatment. METHODS: Fifteen HCC and twelve paracancerous samples underwent chromatin immunoprecipitation (ChIP) sequencing targeting H3K27ac, and subsequently the SEs were identified by the Rank Ordering of Super-Enhancers algorithm. Differential SEs featured by tumor or paracancerous tissues were identified, and cross-referenced with the differential expression genes and prognosis-related genes in 2 independent public or in-house HCC cohorts. The SE region of HSPA4 was deleted in the genome of HCCLM3 cell by CRISPR-Cas9, named HSPA4-SE-KO cells. The potential druggable transcriptional factors were identified by CRCmapper, GeneMANIA and Drug Gene Interaction Database (DGID). RESULTS: Five targets, including CDKN2C, HSPA4, GGH, PDGFA, and CAP2, were identified as HCC-gain SEs with oncogenic potential, which were further validated experimentally by SE inhibitors and ChIP targeting H3K27ac and BRD4. Cell proliferation and migration assays further confirmed that silencing of these HCC-gain SEs significantly suppressed the malignant phenotype of HCC cell lines. HSPA4 appeared strongest oncogenic functions among these targets, which was further verified by HCC mouse xenograft models and clinical sample investigation. Moreover, HSPA4-SE-KO cells obtained significantly suppressed HSPA4 expression and retarded tumorigenic capability. Finally, dysregulation of transcriptional factors engaged in the oncogenic role of SEs, and Danthron that targeting RXRA were identified from DGID for HCC treatment. CONCLUSION: The dysregulated SE landscape of HCC promoted the malignancy phenotype by the upregulation of oncogenes, and SE-regulatory network might be potential drug targets for HCC treatment. Our study deepened the insight of epigenetic dysregulation in HCC, offering the groundwork for SEs as potential therapeutic targets of HCC treatment.

Humans↗