MESH1 functions as a metazoan PAPS phosphatase to regulate sulfation

Nature Chemical Biology · 2026-04-10

Expression Analysis of a Bilin-binding Protein Gene in Relation to Green and Yellow Larval Coloration in Antheraea pernyi

Biotechnology Journal International · 2026-03-26

Background: The larval color patterns of the wild silkworm Antheraea pernyi (Lepidoptera: Saturniidae) exhibit high diversity. However, the molecular basis underlying larval pigmentation in this species remains poorly understood and little pigment-related genes has been characterized so far. Aims: The aim of this study is to determine the role of BBP2 in the differentiation of body color in the larvae of Antheraea pernyi. Study Design: The F2 generation larvae obtained from the cross between A. pernyi strains Xuanda (green) and Shenhuang No. 1 (yellow) were analyzed to evaluate the inheritance pattern of larval coloration and the expression profile of BBP2. Place: College of Bioscience and Biotechnology. Methodology: Hemocyte, fat body, midgut, silk gland, and integument were obtained from 5-6 green and yellow 5th larvae of F2 generation, respectively. Quantitative real-time PCR (qRT-PCR) was performed to determine the relative expression levels of BBP2 across different tissues. Results: The inheritance of green and yellow body color follows Mendelian segregation. However, no significant differences in BBP2 expression were detected between green and yellow larvae in more of the tissues analyzed. Conclusions: BBP2 may not play key roles in regulating the formation of green and yellow body coloration in A. pernyi larvae.

H2O2-GA3-Na2WO4 Synergistically Promotes Germination of Immature Winter Wheat Grains for Speed Breeding

Plants · 2026-04-24

Seed germination is a critical initial stage of the plant life cycle, regulated by signaling pathways such as phytohormones and reactive oxygen species (ROS). However, the low germination rate of immature grains is a key bottleneck limiting wheat speed breeding. This study used immature grains of the winter wheat cultivar Kenong 199 (KN199) collected 18 days post anthesis to establish an efficient germination protocol. By screening individual and combined treatments of hydrogen peroxide (H2O2, 1%), gibberellin (GA3, 20 μM), and varying concentrations of abscisic acid (ABA) synthesis inhibitor sodium tungstate (Na2WO4), alongside transcriptome analysis, we identified the optimal reagent combination and gained preliminary insight into its molecular basis. The triple reagent combination of 0.5 mM Na2WO4 + 20 μM GA3 + 1% H2O2 exhibited the highest germination rate of 80%, approximately sevenfold higher than single reagent treatments, with germination rate peaking after 4 days. Transcriptome profiling revealed that this combination modulated the expression of key genes related to dormancy release and germination, including upregulation of GA biosynthesis gene GA3ox2 and ABA catabolism gene TaCYP707A2, and downregulation of ABA biosynthesis and signaling genes (ABI5, TaNCED1, etc.). Additionally, genes associated with energy metabolism and transport pathways were enhanced. This optimized reagent combination significantly improves immature grain germination, shortens the breeding cycle, and provides a practical tool for achieving “five generations per year” speed breeding in winter wheat. Our findings contribute to seed biology by offering a chemical strategy to overcome dormancy in immature cereal grains.

ZWINT down-regulated by miR-495-3p inhibited lung metastasis of breast cancer by blocking p38 MAPK signaling pathway activation

Human Cell · 2025-10-04

Breast cancer metastasis is the primary cause of patient mortality, yet effective therapeutic targets remain limited. Building on our prior identification of ZWINT as a prognostic marker linked to metastasis, this study defines its critical functional role and regulatory mechanism. Multi-omics analysis revealed a strong association between ZWINT expression and metastatic processes across breast cancer subtypes. Functionally, ZWINT knockdown significantly inhibited breast cancer cell migration and invasion in vitro and dramatically reduced lung metastasis in vivo. Mechanistically, we discovered that miR-495-3p directly targets and suppresses ZWINT expression, and this miR-495-3p/ZWINT axis acts through inhibiting p38 MAPK pathway activation to suppress metastatic progression in vitro. Our findings demonstrate that ZWINT drives breast cancer metastasis and is negatively regulated by miR-495-3p. The newly identified miR-495-3p/ZWINT/p38 MAPK axis may provide a promising therapeutic target for suppressing breast cancer progression.

METRN modulates immune escape via CD8+ T cells in breast cancer progression through IL-6 signaling pathway

Translational Cancer Research · 2025-09-01

Background: Breast cancer remains one of the most prevalent and lethal cancers among women, with a notable risk of recurrence and metastasis. Meteorin (METRN) is a newly discovered cytokine that plays a critical role in neurodevelopment and immune regulation. However, its involvement in breast cancer, particularly in modulating the immune microenvironment, is not well understood. This study aims to investigate the role of METRN in breast cancer progression and to elucidate its potential function in regulating interleukin-6 (IL-6)-mediated cluster of differentiation 8 positive (CD8+) T cell activity. Methods: We used bioinformatics tools to analyze METRN’s diagnostic and prognostic value in breast cancer, validated the findings with clinical samples, and examined METRN’s effects on cell behavior using MCF-7, MDA-MB-231, and SKBR3 cell lines. We assessed cell proliferation, migration, invasion, and apoptosis, and studied METRN’s interaction with IL-6 in modulating CD8+ T cell function using enzyme-linked immunosorbent assay (ELISA) and quantitative PCR (qPCR). In vivo, tumor growth was evaluated in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice, which lack adaptive immunity and thus reflect tumor cell-intrinsic effects. Results: Bioinformatics analysis showed that METRN was highly expressed in breast cancer and correlated with poor prognosis. METRN inhibition reduced tumor cell proliferation, migration and invasion, while increasing apoptosis. In vitro co-culture assays showed that METRN knockdown increased IL-6 production and enhanced CD8+ T-cell effector function, whereas IL-6 silencing abrogated these effects. CD8 staining was also performed and was shown for completeness. However, given that NOD/SCID mice lacked adaptive immunity, these signals cannot be interpreted as functional CD8+ T-cell infiltration, but were presented as technical staining results. Conclusions: METRN promotes breast cancer progression through tumor-intrinsic mechanisms, while in vitro and bioinformatics analyses further indicate that METRN regulates IL-6-linked CD8+ T-cell activity. These findings highlight METRN as a potential biomarker and therapeutic target in breast cancer, while further validation in immunocompetent or humanized mouse models will be required to assess its role in immunotherapy.

Heat shock proteins function as signaling molecules to mediate neuron–glia communication in C. elegans during aging

Nature Neuroscience · 2025-06-18 · 12 citations

MicroRNA-32-5p promotes the proliferation and metastasis of gastric cancer cells

Scientific Reports · 2025-01-17 · 2 citations

Gastric cancer (GC) is a huge threat to global health, there is no effective treatment or just delay the progression of advanced GC until now. Micro-RNAs were reported to participate in the progression of GC. Clonal formation, MTT, caspase-3 activity, sperm DNA fragmentation, flow cytometry assay, cell adhesion, transwell assays were performed to detect the functions of miR-32-5p or anti-miR-32-5p on the growth and metastasis of GC cells. Western blot, qRT-PCR, Co-immunoprecipitation, and luciferase reporter analysis were performed to explore the associated mechanisms. We established mouse tumor xenografts and mouse metastasis models to explore the role of miR-32-5p and anti-miR-32-5p in vivo. We found that miR-32-5p significantly promoting the proliferation and metastasis of GC cells at both in vitro and in vivo levels. The underlying mechanism maybe that miR-32-5p complementary paired with the 3'-UTR of DSC2, and inhibited the expression of DSC2. Furthermore, we found that DSC2 suppressed the transcription of Cyclin B1, and induced G2/M phase arrest through inhibiting the complex of β-catenin/TCF4 in nucleus. We concluded that miR-32-5p negatively regulated the DSC2 expression, might be a potential therapeutic targeting of cancers, most especially in GC.

Injury-induced nuclear export of RNA-binding proteins drives mRNA stabilization and translation to promote dendrite regeneration

bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-18

Summary Dendrite regeneration is critical for restoring neuronal connectivity after injury, yet the underlying molecular mechanisms remain poorly understood. Using C. elegans as a model and through a forward genetic screen, we identified the conserved insulin degrading enzyme idr-1 and the RNA-binding protein rbm-42 as key regulators of dendrite regeneration, where idr-1 functions upstream of rbm-42 . We further show that ced-7 , one of the core components of the phagocytosis pathway, acting down stream of rbm-42 , while other components of this pathway don’t play significant roles in dendrite regeneration. In addition, we demonstrate that upon injury IDR-1 can promote RBM-42 nuclear export following injury, enabling its dendritic localization. RBM-42, in turn, promotes the translation of ced-7 and facilitates microtubule assembly. In conclusion, our findings define a novel conserved signaling cascade coupling injury-induced nuclear export of RNA binding proteins to local regulation and dendrite regeneration, providing new mechanistic insight into neuronal repair.

Hyperglycemia induces an immunosuppressive microenvironment in colorectal cancer liver metastases by recruiting peripheral blood monocytes through the CCL3-CCR1 axis

Journal for ImmunoTherapy of Cancer · 2025-06-01 · 11 citations

BACKGROUND: The treatment of colorectal cancer liver metastasis (CRLM), a leading cause of mortality in patients with colorectal cancer, is complicated by type 2 diabetes (T2D). This study aimed to investigate the CRLM immune microenvironment in the context of T2D and identify potential therapeutic targets. METHODS: A hyperglycemic CRLM mouse model was established. Seven single-cell RNA sequencing datasets were analyzed, including three peripheral blood mononuclear cells (PBMCs) datasets (from healthy donors and T2D patients) and four datasets with 20 CRLM samples and matching PBMCs datasets, to explore the immune characteristics and remodeling of the tumor microenvironment in CRLM with concurrent T2D. RESULTS: T cell subpopulations were also altered, and the number of myeloid cells and their function was increased. Myeloid cells in CRLM from patients with T2D exhibited high expression levels of CCL3, which recruited peripheral blood monocytes expressing high levels of CCR1, leading to an accumulation of myeloid cells and an immunosuppressive tumor microenvironment. Recruited cells exhibited enhanced T cell communication abilities, indicating an augmented immunosuppressive capacity. In addition, CCR1 expression in peripheral blood monocytes from patients with CRLM was closely correlated with the immunosuppressive tumor microenvironment, suggesting that CCR1 expression levels may predict immune cell phenotype and prognosis in patients with CRLM and T2D. CONCLUSIONS: Our study revealed complex changes in the tumor microenvironment of patients with CRLM and T2D. In particular, a novel mechanism was identified by which hyperglycemia regulates immunosuppression: the CCL3-CCR1 signaling axis. This finding offers a novel potential therapeutic target for patients with CRLM and T2D and provides an important theoretical basis for the future prediction of the prognosis of these patients.

The wheat transcription factor Q functions in gibberellin biosynthesis and signaling and regulates height and spike length

The Plant Cell · 2025-07-29 · 7 citations

The Q gene is a key domestication gene in wheat (Triticum aestivum) that regulates free-threshing habit, spike morphology, height, and other critical agronomic traits. However, the precise molecular mechanisms underlying its function remain unclear. In this study, we identified a Q allele with a missense mutation (G to A) in the fifth exon of the Q gene, resulting in reduced plant height and spike length. Further investigation revealed that this mutation causes a Gly-229-Ser amino acid substitution, which enhances Q protein stability. Furthermore, we discovered that Q directly binds to the promoter region of Gibberellin 3-oxidase 2 gene (TaGA3ox2) and represses its expression. Moreover, Q interacts with both REDUCED HEIGHT1 (RHT1) and GIBBERELLIN INSENSITIVE 2 (TaGID2), which may disrupt GID2-triggered RHT1 degradation. Collectively, these findings reveal the dual roles of Q in regulating both GA biosynthesis and signaling, providing insights into the molecular mechanisms through which Q modulates plant height and spike length in wheat.