Biomedical subjects

Meng Liu

Publications and source records attributed to Meng Liu.

5 recordsLinked to original sources

PubMed2026

The H3K27me3 reader GmLHP1 impairs Phytophthora sojae resistance by repressing ethylene precursor accumulation in soybean.

Phytophthora root rot, caused by Phytophthora sojae, is a devastating soilborne disease of soybean (Glycine max). However, the epigenetic regulation of soybean responses to P. sojae remains incompletely understood. Here, using genetic, molecular and biochemical approaches, we characterized the functions of LIKE HETEROCHROMATIN PROTEIN 1 (GmLHP1) and its downstream regulatory network. We demonstrated that GmLHP1, as a reader of H3K27me3, negatively regulates soybean resistance to P. sojae. GmLHP1 binds to H3K27me3 peptides in vitro and colocalizes with H3K27me3 marks genome-wide in vivo. The integrated chromatin immunoprecipitation sequencing and RNA sequencing analysis identified the ethylene biosynthesis pathway gene 1-AMINO-CYCLOPROPANE-1-CARBOXYLATE SYNTHASE 18 (GmACS18) as being enriched for H3K27me3 and bound by GmLHP1, leading to its transcriptional downregulation. Notably, GmLHP1 associates with the GmACS18 promoter by directly binding to AATTAA motifs and recognizing H3K27me3 marks. Moreover, GmACS18 enhances defense against P. sojae by accumulating the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC). Further analysis unveiled that recognition of H3K27me3 by GmLHP1 is essential for regulating soybean resistance to P. sojae through repressing GmACS18 transcription and decreasing ACC accumulation. Our findings reveal a novel epigenetic regulatory mechanism in which the H3K27me3 reader GmLHP1 blocks soybean resistance to P. sojae by repressing ethylene precursor ACC accumulation.

ACC accumulation↗

PubMed2026

Targeting PRMT9 overcomes venetoclax resistance in AML by modulating splicing and inhibiting translation.

Arginine methylation catalyzed by protein arginine methyltransferases (PRMTs) is required for cancer cell proliferation, but whether PRMTs mediate resistance to therapy remains unclear. Here, we performed loss-of-function screens in venetoclax-resistant (VEN-R) acute myeloid leukemia (AML) patient-derived xenograft cells and found that PRMT9 plays a critical role in promoting VEN resistance. Specifically, VEN-R AML samples exhibited high levels of PRMT9, and PRMT9 inhibition resensitized AML cells to VEN treatment. In preclinical resistant models, genetic ablation of PRMT9 synergized with VEN to eradicate AML cells. Consistently, pharmacologic inhibition of PRMT9 combined with VEN produced similar effects in VEN-R AML mouse models. Mechanistically, PRMT9 ablation disrupted RNA splicing by inducing exon skipping in mRNA encoding ALG13, an uridine diphosphate (UDP)-N-acetylglucosaminyltransferase subunit, thereby downregulating expression of the VEN efflux transporter encoded by the adenosine triphosphate-binding cassette subfamily C member 1 gene. PRMT9 inhibition also suppressed protein synthesis, leading to downregulation of short-lived oncoproteins such as MCL1. These findings establish a connection between PRMT9-mediated arginine methylation and poor VEN responsiveness and demonstrate that targeting PRMT9 may represent a viable strategy to overcome VEN resistance.

Protein-Arginine N-Methyltransferases↗

PubMed2026

Human Wings Apart-Like Protein as a Serum Diagnostic Biomarker in Cervical Cancer: An Integrative Bioinformatics Analysis with Serum Validation.

Cervical cancer remains a major threat to women's health worldwide, and reliable serum biomarkers for early detection and therapeutic stratification remain limited. Human wings-apart-like (hWAPL) protein has been implicated in cervical carcinogenesis, but its diagnostic and clinical value has not been fully elucidated. To address this gap, this study integrated public multi-omics datasets, including The Cancer Genome Atlas, GEPIA2, the Human Protein Atlas, and single-cell transcriptomic data, to characterize hWAPL expression, clinicopathological associations, immune infiltration, co-expression networks, post-translational modifications, and drug sensitivity predictions. These findings were evaluated in an independent single-center serum cohort comprising 89 patients with histologically confirmed cervical squamous cell carcinoma and 89 healthy female controls. Serum hWAPL and squamous cell carcinoma antigen (SCC) levels were measured, and diagnostic performance was assessed by receiver operating characteristic curve analysis. In silico, hWAPL was broadly upregulated across multiple malignancies, particularly cervical cancer, enriched in malignant epithelial cells and monocytes/macrophages, and associated with shorter progression-free interval, predicted reduced sensitivity to cisplatin, paclitaxel, and 5-fluorouracil, and predicted sensitivity to MCL-1 and Wee1 inhibitors. In the serum cohort, hWAPL levels were significantly higher in patients than controls and discriminated cervical cancer with an area under the curve of 0.961, exceeding SCC alone. Combining hWAPL with SCC further improved diagnostic performance (area under the curve, 0.974; sensitivity, 93.3%; specificity, 95.5%). These findings suggest that serum hWAPL is a potential novel diagnostic biomarker for cervical squamous cell carcinoma whose performance is enhanced by SCC, whereas the observed associations with chemoresistance and immune microenvironment remodeling are hypothesis-generating and require experimental confirmation.

Humans↗

PubMed2026

Stepwise allelic trajectory of ETP2 underlies trade-off between UVB tolerance and submergence adaptation in Arabidopsis thaliana.

Strong UVB radiation critically restricts plant growth, yield, and distribution, while mechanisms enabling adaptation to intense UVB remain unclear. Here, we uncover that the F-box ubiquitin E3 ligase UVBT1 (also known as ETP2) is indispensable for UVB tolerance in A. thaliana. In the high-altitude Tibet accession, a distinctive 166-bp deletion in ETP2 promoter leads to the complete absence of the W-box element, thereby eliminating WRKY36-mediated transcriptional repression. This results in elevated ETP2 levels, which degrade EIN2 and activate the protective anthocyanin/flavonoid pathway. Conversely, in low-altitude accessions, which are often exposed to lower UVB and higher precipitation conditions, WRKY36-mediated repression of ETP2 stabilizes EIN2 and WRKY22, endowing the plants with submergence tolerance. Notably, aside from the Tibet-accession-specific 166-bp deletion, the geographical distribution of the promoter allelic shift from C to G near the ETP2 W-box within the 166-bp region is tightly associated with UVB radiation with increasing altitudes for the other global accessions. This allelic change also enhances WRKY36-mediated repression of ETP2, suggesting an additional stepwise adaptation process. This work thus defines the WRKY36-ETP2-EIN2/WRKY22 module as a key regulator of UVB tolerance and submergence adaptation, potentially enabling A. thaliana to adapt to environments with varying UVB and precipitation conditions.

Arabidopsis↗

PubMed2025

Cytogenetics and genomics analysis of cold-hardy perennial wheatgrass: insights into agronomic performance, chromosome composition, and gene expression.

Intermedium wheatgrass (Thinopyrum intermedium), a perennial species with extensive root systems and high tolerance to cold, drought, and salinity, is a valuable genetic resource for the development of perennial crops. Over a decade-long selection process, two cold-hardy perennial wheatgrass lines were developed by crossing wheat-Thinopyrum partial amphiploids with Th. intermedium. These lines inherited key traits from Th. intermedium, including plant stature, spike morphology, and postharvest regrowth. Transcriptome-based single-nucleotide polymorphism tracing and sequential multicolor genomic in situ hybridization analyses revealed variations in the chromosome compositions of the perennial wheatgrass lines. The introgression of wheat chromosomes enhanced grain weight and size, while preserving the cold-hardy, perennial characteristics of the wheatgrass lines compared to Th. intermedium. Genome-wide gene expression was generally suppressed in the wheatgrass lines relative to Th. intermedium, particularly in conserved genes. This suppression was especially pronounced in genes involved in cell division and DNA repair pathways. In contrast, genes associated with cold tolerance and the water stress response were upregulated. We identified eight cold-tolerance genes in the Th. intermedium chromosomes and validated three of them, Thint.J05G452200, Thint.J05G452300, and Thint.V05G408900, using qRT-PCR. These genes encode proteins associated with cold tolerance and are potential candidates for further functional validation. Additionally, three chromosomes from homoeologous group 6 were introgressed, carrying six genes potentially associated with superior grain traits. Among them, TraesCS6D02G287800, which encodes a specific protein, exhibited high expression levels in both wheatgrass lines, suggesting its critical role in enhancing grain traits. Our results indicate that the suppression of grass gene expression, likely due to the introgression of wheat chromosomes and the upregulation of pathways related to cold tolerance and overwintering ability, contributes to the adaptive features of the wheatgrass lines. This study provides a genomic foundation for understanding gene expression regulation in distant hybrid progeny and offers valuable insights for designing new breeding strategies for perennial wheat or wheatgrass.

Chromosomes, Plant↗