PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2024
·
IF 4.2
Ming Liu,Qianwen Wang,Bin Lai,Yan Chen,Rongchumu Ge,Shuo Yan,Chunya Bu
β- N -acetylhexosaminidases (HEXs) are key chitin-degrading enzymes in insects. Here, we identified TuHex1 and TuHex2 using insect orthologous genes by searching Tetranychus urticae genome and transcriptome database to investigate their roles in mite molting. TuHex1 and TuHex2 expression was induced by 20-hydroxyecdysone (20E), and inhibition of TuHex1 and TuHex2 expression by RNAi resulted in wrinkled cuticle or an inability to shed the old cuticle in nymphs, which may be due to a reduction in particle deposition in the exocuticle and lamellar structure in the endocuticle as revealed by scanning electron microscopy and transmission electron microscopy. The results suggest that the TuHex1 and TuHex2 genes play an essential role in the molting and developmental process of the mite. TuHex2 , with a mortality rate of 67.41 % in the leaf disc assay, was a potential RNAi target by oral feeding. Spraying of nanocarrier-delivered bacteria expressing ds TuHex2 at 500 ng/μL kept spider mites at a consistently low level throughout the 14 days and showed good mite control comparable to that of matrine. In addition, nanocarrier-delivered ds TuHex2 is safe for Neoseiulus californicus in our experiments, providing its potential for green mite management.
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PubMed
高影响因子
Small
·
2018
·Vol. 14
·期 10
·1703858
·
IF 9.598
Keying Zhang,Lin Yang,Feng Lu,Xingcai Wu,Jun-Jie Zhu
Here, a sensitive and universal noncoding RNA (ncRNA) upconversion sensing nanoplatform is developed. Gold nanoparticles bearing one hairpin DNA (Hp) molecule are conjugated to the linker DNA modified NaYF 4 :Yb, Er@NaYF 4 upconversion nanoparticles by DNA hybridization, leading to quenching of the upconversion emission through fluorescence resonance energy transfer. A signal DNA (SDNA) sequence is designed to open Hp, recovering the upconversion emission. To achieve universality and high sensitivity of the nanoprobe, an exonuclease III (Exo III)-assisted cycling amplification strategy is introduced. A multifunctional hairpin DNA (mHp) containing ncRNA recognition sequence and SDNA sequence is designed to recognize ncRNA and trigger Exo III as a biocatalyst to stepwise disintegrate itself, releasing both ncRNA and SDNA. The released ncRNA can be reused to release more SDNA, which greatly improves the sensing sensitivity. By changing the recognition portion of mHp, various ncRNA can be detected. The sensitive detection of both homeobox (HOX) transcript antisense RNA segment and miR-21 is achieved with this novel strategy, even in human serum, indicating the universality and sensitivity of the proposed strategy. Additionally, the expression level of miR-21 in human breast cancer cell (MCF-7) lysate is successfully measured, suggesting its potential in clinical diagnosis.
研究领域:
生物技术
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纳米技术
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癌症诊断
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分子生物学
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PubMed
高影响因子
CHEMISTRY OF MATERIALS
·
2026
·
IF 7.1
Renpeng Xia,Jiarong Guo,Jinwen Zhu,Peng Miao
RNA interference has garnered significant interest as a type of nucleic acid therapeutics. MicroRNA (miRNA)-mediated mRNA modulation and gene therapy have yielded promising progress. However, clinical application is impeded by low delivery efficiency and insufficient targeting specificity. We herein develop a hybrid membrane-based delivery system with a magnetic core and spatially isolated functional nucleic acid strands. Due to the hybrid lipid bilayer, CD47-mediated immune evasion and galectin-3-mediated homologous targeting facilitate effective delivery of nucleic acids and magnetic nanomaterials. The membranes effectively protect these antitumor reagents during transportation. After internalization inside tumor sites, the strand displacement reaction between the nucleic acids successfully releases miR-200c, which stimulates inflammatory cytokine secretion and modulates apoptotic cytokine expression. Meanwhile, the acidic microenvironment dissociates Fe2+ from the magnetic core and initiates the Fenton reaction to amplify cytotoxic oxidative damage. The two pathways thereby confer robust antitumor efficacy with synergistic effects, which have great potential for future clinical translation.
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CLINICAL & EXPERIMENTAL METASTASIS
·
2026
·Vol. 43
·期 4
·34
·
IF 3.7
Dong Chenglai,Zhu Deqi,Zhang Jincao,Gan Shaoyin,Zhao Jia,Li Chunlin,Li Bin
Metastasis contributes to treatment failure and poor prognosis of esophageal squamous cell carcinoma (ESCC) patients. The 5’-3’ exoribonuclease 2 (XRN2) is related to the pathogenesis and progression of various malignancies through its roles in transcription termination and metastasis promotion, but its function in ESCC remains unclear. Bioinformatic analysis showed that XRN2 was significantly overexpressed in ESCC tissues and was identified as a risk factor for ESCC patients. The analysis of our own cohort confirmed that XRN2 expression was overexpressed and significantly correlated with cancer stage in patients ( P = 0.0100). Gain- and loss- of function analyses revealed that XRN2 promoted ESCC cell growth, migration and invasion capabilities, as well as experimental lung colonization foci. Interestingly, we found that the RNA level of XRN2 was upregulated by the RNA-binding protein polypyrimidine tract binding protein 3 (PTBP3). Specifically, PTBP3 bound to CUUUC motifs of the 3’UTR of XRN2, prolonging the half-life of XRN2 RNA. PTBP3 was found to be significantly overexpressed in ESCC, where its expression level correlated with tumor stage ( P = 0.0164) and tumor size ( P = 0.0495), positioning it as a risk factor for ESCC patients. PTBP3 upregulation promoted ESCC cell growth, migration, and invasion in vitro and in vivo. Notably, knockdown of XRN2 reversed the tumor promotion effects induced by PTBP3 overexpression. Collectively, our data reveal a novel function of XRN2 in ESCC metastasis and the critical roles of the PTBP3/XRN2 axis in ESCC metastasis, highlighting its promise as a novel therapeutic target in ESCC. Graphical abstract
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高影响因子
PLANT PHYSIOLOGY
·
2026
·
IF 8.2
Liu Yuhan,Zheng Yutong,Jiang Deyuan,Shi Yafei,He Kaixiang,Ke Xiangsheng,Wang Yetao,Liu Xinlian,Hou Xin
Chloroplast-to-nucleus retrograde signaling and plastid RNA editing are both essential for chloroplast biogenesis and plant development, but the underlying mechanism linking these two processes remains unclear. Here, we identify the mitochondrial transcription termination factor mTERF3/Seedling Lethal 1 (SL1), previously characterized as a plastid-encoded RNA polymerase (PEP)-associated protein, as a key regulator connecting RNA editing to retrograde signaling. SL1 directly interacts with GUN1 and MORF2 and is indispensable for 31 out of 34 plastid RNA editing sites in Arabidopsis. Loss of SL1 function results in a strong genome uncoupled (gun) molecular phenotype under norflurazon (NF) treatment, accompanied by defective RNA editing and complete loss of the NDH complex. Mechanistically, SL1 assembles the editosome by recruiting canonical and atypical PPR-DYW proteins (CRR28, RARE1, DYW1, and DYW2) together with multiple non-PPR editing factors, while its strong affinity to MORF2 ensures appropriate editosome stoichiometry. SL1 also colocalizes with the PEP complex, suggesting a physical coupling between transcription and RNA editing in plastid nucleoids. Furthermore, SL1 modulates RNA editing profiles and regulates GLK1/2 expression during NF-induced retrograde signaling. Our findings expand the functional repertoire of mTERF proteins and uncover a molecular mechanism that connects RNA editing with retrograde signaling through SL1.
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高影响因子
Nature Communications
·
2026
·Vol. 17
·期 1
·2565
·
IF 18.1
He Mingbin,Wang Weiwei,Zhou Haiwu,Liu Cong,Zhao Chunbei,Li Jian,Han Yuewen,Qin Yali,Chen Mingzhou
Pyroptosis plays a crucial role in immune defense against infections and endogenous threats by eliminating harmful cells and modulating the immune response through inflammation. However, the natural activation of pyroptosis involves intricate signaling pathways, posing significant challenges for its artificial manipulation in research and therapies. Here, we present DAMAGE ( D e a th Ma nipulation Ge ne), an innovative system that integrates gasdermins within the type III-E CRISPR framework, enabling the specific recognition of target RNA (tgRNA) and triggering pyroptosis. This mechanism allows DAMAGE to selectively identify and eliminate virus-infected, cancerous, and senescent cells, all of which exhibit altered RNA transcriptomes. Additionally, DAMAGE exhibits considerable promise as a platform for mRNA-LNP therapy. Our study highlights the potential of this CRISPR-based system in the controllable induction of pyroptosis, offering an innovative therapeutic strategy for treating RNA-heterogeneous diseases.
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STAR Protocols
·
2026
·Vol. 7
·期 2
·104484
·
IF 1.4
Qiuyao Guo,Wanqing Li,Weiqiang Zheng,Meng Qiu,Chengtian Zhao
Summary Here, we present a protocol for gene knockdown in Trichoplax adhaerens using a silica nanoparticle-mediated RNA interference (RNAi) technique. We describe steps for preparing silica nanoparticles, assembling RNAi complexes, and delivering them to live specimens. This protocol enables reproducible suppression of target gene expression in T. adhaerens and achieves transcript knockdown efficiencies of approximately 50%–70%, as assessed by quantitative PCR. For complete details on the use and execution of this protocol, please refer to Li et al. 1
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高影响因子
Journal for ImmunoTherapy of Cancer
·
2025
·Vol. 13
·期 9
·e011893
·
IF 10.6
Zhengning Yang,Zhongxuan Meng,Shangyuan Liu,Yuxin Chen,Xuhong Gan,Zi‑Mei Zhang,Xiaoshan Luo,Jiahong Yan,Huijin Chen,Danqing Huang,Lihong Huang,Xiaomin Zeng,Wenyu Ma,Jun Liu,Linlin Wang,Haotian Huang,Xinyi Yang,Mei Hu,Lin Chen,Hongli Du,Qibin Leng,Li Qiu,Xiaoling Wang
Background Nonsense-mediated messenger RNA decay (NMD) is a highly conserved surveillance system that degrades mRNAs with premature termination codons (PTCs), and regulates the mRNA quantity. Cancer cells hijack NMD to compensate for the imbalanced DNA levels and modulate their antigenicity. We identified the LTO1/YAE1 complex as NMD factors regulating ribosome biogenesis. Our study aimed to investigate their roles in modulating NMD and major histocompatibility complex class I (MHC-I) antigen presentation, which is vital for cancer immunotherapy. Methods Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated protein 9 (Cas9)-mediated gene knockouts, overexpression, and mutational analysis were used to explore the role of LTO1 and YAE1 in NMD and MHC-I expression across various tumor cell lines, assayed by fluorescent reporter-based assays, fluorescence-activated cell sorting analysis, reverse transcription-quantitative PCR, mRNA decay assay, and polysome profiling. Transcriptomic analyses were used to assess the expression of LTO1/YAE1 and their correlation with MHC-I molecules in human cancers. T cell receptor (TCR)-T cells and tumor cells coculture were employed to monitor the effect of LTO1 and YAE1 loss on T cell activation. Iron chelators were further tested as NMD inhibitors to enhance cancer immunotherapy using in vitro coculture assay and a mouse tumor model for immune checkpoint blockade (ICB) therapy. Results We demonstrate that deficiency in LTO1, YAE1, or their downstream target ABCE1 impairs NMD, causes the overexpression of key regulators of MHC-I, including NLR family CARD domain containing 5 (NLRC5), interferon regulatory factor 1 (IRF1), and nuclear factor-kappa B (NFκB), which results in enhanced T cell activation and tumor cell killing in TCR-T models. Transcriptomic analyses reveal that the LTO1/YAE1 complex is frequently overexpressed in human cancers, where it negatively regulates MHC-I. Moreover, low doses of iron chelators inhibit NMD and enhance MHC-I expression, leading to improved recognition and activation of CD8 + T cells, thereby promoting antigen-specific killing and increasing the efficacy of TCR-T and ICB therapy. Conclusions Collectively, our findings establish novel roles for the LTO1/YAE1 complex in regulating MHC-I expression via NMD. As MHC-I is crucial for antigen presentation and T cell activation, these results reveal a previously unappreciated link between NMD and tumor immunogenicity, with potential implications for cancer immunotherapies.
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高影响因子
CELL
·
2025
·
IF 42.5
Ziqiang Zhou,Shicong Zhu,Yaqiang Hong,Guangpu Jin,Rui Ma,Fan Lin,Yiyang Zhang,Hsiang-Ying Lee,Nian Liu
Discrete genomic units can recombine into composite transposons that transcribe and transpose as single units, but their regulation and function are not fully understood. We report that composite transposons harbor bivalent histone marks, with activating and repressive marks in distinct regions. Genome-wide CRISPR-Cas9 screening, using a reporter driven by the hominid-specific composite transposon SVA (SINE [short interspersed nuclear element]-VNTR [variable number of tandem repeats]-Alu) in human cells, identified diverse genes that modify bivalent histone marks to regulate SVA transcription. SVA transcripts are critical for SVA’s cis -regulatory function in selectively contacting and activating long-range gene expression. Remarkably, a subset of bivalent SVAs is activated during erythropoiesis to boost multiple erythroid gene expression, and knocking down these SVAs leads to deficient erythropoiesis. The RNA-dependent cis -regulatory function of SVA activates genes for myelopoiesis and can contribute to aging-associated myeloid-biased hematopoiesis. These results reveal that the cis -regulatory functions of composite transposons are bivalently regulated to control cell fate transitions in development and aging.
研究领域:
分子生物学
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遗传学
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表观遗传学
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发育生物学
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细胞生物学
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血液学
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衰老研究
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高影响因子
PeerJ
·
2023
·
IF 2.7
Wanwei Hou,Xiaojuan Zhang,Yuling Liu,Yujiao Liu,Bai li Feng
Background Faba bean ( Vicia faba L) is one of the most important legumes in the world. However, there is relatively little genomic information available for this species owing to its large genome. The lack of data impedes the discovery of molecular markers and subsequent genetic research in faba bean. The objective of this study was to analyze the faba bean transcriptome, and to develop simple sequence repeat (SSR) markers to determine the genetic diversity of 226 faba bean varieties derived from different regions in China. Methods Faba bean varieties with different phenotype were used in transcriptome analysis. The functions of the unigenes were analyzed using various database. SSR markers were developed and the polymorphic markers were selected to conduct genetic diversity analysis. Results A total of 92.43 Gb of sequencing data was obtained in this study, and 133,487 unigene sequences with a total length of 178,152,541 bp were assembled. A total of 5,200 SSR markers were developed on the basis of RNA-Seq analysis. Then, 200 SSR markers were used to evaluate polymorphisms. In total, 103 (51.5%) SSR markers showed significant and repeatable bands between different faba bean varieties. Clustering analysis revealed that 226 faba bean materials were divided into five groups. Genetic diversity analysis revealed that the relationship between different faba beans in China was related, especially in the same region. These results provided a valuable data resource for annotating genes to different categories and developing SSR markers.
研究领域:
植物学
·
遗传学
·
分子生物学
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高影响因子
Frontiers in Cell and Developmental Biology
·
2023
·
IF 5.5
Yang Xiancong,Wang Yaoyao,Rong Simin,An Jiayue,Lan Xiaoxu,Yin Baohui,Sun Yunxiao,Wang Pingyu,Tan Boyu,Xuan Ye,Xie Shuyang,Su Zhenguo,Li Youjie
Introduction: Acute myeloid leukemia (AML) is a malignant proliferative disease affecting the bone marrow hematopoietic system and has a poor long-term outcome. Exploring genes that affect the malignant proliferation of AML cells can facilitate the accurate diagnosis and treatment of AML. Studies have confirmed that circular RNA (circRNA) is positively correlated with its linear gene expression. Therefore, by exploring the effect of SH3BGRL3 on the malignant proliferation of leukemia, we further studied the role of circRNA produced by its exon cyclization in the occurrence and development of tumors.Methods: Genes with protein-coding function obtained from the TCGA database. we detected the expression of SH3BGRL3 and circRNA_0010984 by real-time quantitative polymerase chain reaction (qRT-PCR). We synthesized plasmid vectors and carried out cell experiments, including cell proliferation, cell cycle and cell differentiation by cell transfection. We also studied the transfection plasmid vector (PLVX-SHRNA2-PURO) combined with a drug (daunorubicin) to observe the therapeutic effect. The miR-375 binding site of circRNA_0010984 was queried using the circinteractome databases, and the relationship was validated by RNA immunoprecipitation and Dual-luciferase reporter assay. Finally, a protein-protein interaction network was constructed with a STRING database. GO and KEGG functional enrichment identified mRNA-related functions and signaling pathways regulated by miR-375.Results: We identified the related gene SH3BGRL3 in AML and explored the circRNA_0010984 produced by its cyclization. It has a certain effect on the disease progression. In addition, we verified the function of circRNA_0010984. We found that circSH3BGRL3 knockdown specifically inhibited the proliferation of AML cell lines and blocked the cell cycle. We then discussed the related molecular biological mechanisms. CircSH3BGRL3 acts as an endogenous sponge for miR-375 to isolate miR-375 and inhibits its activity, increases the expression of its target YAP1, and ultimately activates the Hippo signaling pathway involved in malignant tumor proliferation.Discussion: We found that SH3BGRL3 and circRNA_0010984 are important to AML. circRNA_0010984 was significantly up-regulated in AML and promoted cell proliferation by regulating miR-375 through molecular sponge action.
研究领域:
肿瘤学
·
分子生物学
·
遗传学
·
癌症研究
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PubMed
高影响因子
International Journal of Electrochemical Science
·
2023
·
IF 1.5
Yang Liu,Yan Huang
MicroRNAs (miRs) are believed to be associated with cancer and serve as a marker of its presence. Detecting miR in body fluid with a high level of sensitivity is a significant factor for disease screening. A point-of-care technology (POCT) based electrochemiluminescence (ECL) biosensor was created with a higher level of sensitivity for the recognition of miR-126. Glutathione-stabilized gold nanoclusters (GSH-Au NCs) were employed as ECL reagents in this study. Potassium persulfate (K 2 S 2 O 8 ) was chosen as the co-reaction reagent. Consequently, we chose the catalytic hairpin self-assembly strategy to attain accurate detection of miR-126. The prepared sensor is able to detect miR-126 linearly from 10 aM to 0.1 nM, and the detection limit is as low as 3.17 aM.
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