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RBM25 depletion suppresses the growth of colon cancer cells through regulating alternative splicing of MNK2

Science China Life Sciences 2024年

作者： Lili Zhi Chaoqun Chen Ge Zhang Tian Huang Wenxia He Jinrui Zhang Dan Chen Jiayi Liu Jinyao Zhao Yangfan Qi Guiying Wang Wenjing Zhang Yang Wang Sino-US research Center for Cancer Translational Medicine of the Second Affiliated Hospital of Dalian Medical University&institute of Cancer stem cell Dalian Medical University Department of Immunology College of Basic Medical SciencesDalian Medical University institute of Cancer stem cell Dalian Medical University Department of Pathology the First Affiliated Hospital of Dalian Medical UniversityDalian Medical University Department of General Surgery the Second Hospital of Hebei Medical University The Second Department of General Surgery the Fourth Hospital of Hebei Medical University Hebei Key Laboratory of Etiology Tracing and Individualized Diagnosis and Treatment for Digestive System Carcinoma

Increasing evidence suggests that deregulated RNA splicing factors play critical roles in tumorigenesis;however,their specific involvement in colon cancer remains largely *** we report that the splicing factor RBM25 is overexpressed in colon cancer,and this increased expression correlates with a poor prognosis of patients with colon ***,RBM25 ablation suppresses the growth of colon cancer cells both in vitro and in ***,our transcriptome-wide analysis of splicing events revealed that RBM25regulates a large number of cancer-related alternative splicing events across the human genome in colon ***,RBM25regulates the splicing of MNK2 by interacting with the poly G rich region in exon 14a,thereby inhibiting the selection of the proximal 3′splice site (ss),resulting in the production of the oncogenic short isoform,*** of RBM25 leads to an increase in the MNK2a isoform and a decrease in the MNK2b ***,re-expression of MNK2b or blocking the 3′ss of the alternative exon 14a with ASO partially reverses the RBM25 knockdown mediated tumor ***,MNK2b levels were significantly increased in colon cancer tissues,which is positively correlated with the expression level of ***,our findings uncover the critical role of RBM25 as a key splicing factor in colon cancer,suggesting its potential as a prognostic marker and therapeutic target.

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Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

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Neural Regeneration research 2024年第2期19卷 440-446页

作者： Sumei Liu Baoguo Liu Qian Li Tianqi Zheng Bochao Liu Mo Li Zhiguo Chen cell Therapy Center Beijing Institute of GeriatricsXuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric Diseasesand Key Laboratory of Neurodegenerative DiseasesMinistry of EducationBeijingChina Center of Neural Injury and Repair Beijing Institute for Brain DisordersBeijingChina Center of Parkinson’s Disease Beijing Institute for Brain DisordersBeijingChina

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate *** a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury ***,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord *** neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury ***,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion *** of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the ***,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion ***-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

关键词： biomaterial fibrinogen functional recovery induced neural stem cell transplantation microenvironment microglia spinal cord injury thrombin

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Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina Dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis Laboratory of Developmental Biology Department of Biology University of Patras Laboratory of cellular and Molecular Neurobiology-stem cells Hellenic Pasteur Institute 3. Department of Physiology School of Medicine University of Patras

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the “weaver” mouse, a model of progressive nigrostriatal degeneration. Here, we extended our investigation in two clinically-relevant ways. First, we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors. Second, we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice, at late stages of degeneration. We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells, marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors. In agreement, we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice. However, the graft strongly induced an endogenous neurogenic response throughout the midbrain, which was significantly enhanced by the administration of microneurotrophin BNN-20. Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20. Interestingly, the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells (iPSCs) neurotrophic factors Parkinson's disease substantia

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3'-Deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome

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Neural Regeneration research 2024年第10期19卷 2270-2280页

作者： Yize Qi Yao Zhou Jiyang Li Fangyuan Zhu Gengni Guo Can Wang Man Yu Yijie Wang Tengfei Ma Shanwu Feng Li Zhou institute for stem cell and Neural Regeneration and Key Laboratory of Cardiovascular&Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Anesthesiology The Second People’s Hospital of LianyungangLianyungangJiangsu ProvinceChina Department of Anesthesiology Women’s Hospital of Nanjing Medical UniversityNanjing Maternity and Child Health Care HospitalNanjingJiangsu ProvinceChina

Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.

关键词： 3′-deoxyadenosin hippocampus long-term potentiation methamphetamine NOD-like receptor family pyrin domain containing-3(NLRP3)inflammasome synaptic plasticity

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Single-cell immune landscape of measurable residual disease in acute myeloid leukemia

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Science China Life Sciences 2024年

作者： Xiaodong Mo Weilong Zhang Guomei Fu Yingjun Chang Xiaohui Zhang Lanping Xu Yu Wang Chenhua Yan Mengzhu Shen Qiuxia Wei Changjian Yan Xiaojun Huang Peking University People's Hospital Peking University Institute of Hematology National Clinical Research Center for Hematologic Disease Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Department of Hematology Lymphoma Research Center Peking University Third Hospital Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies Chinese Academy of Medical Sciences

Measurable residual disease(MRD) is a powerful prognostic factor of relapse in acute myeloid leukemia(AML). We applied the single-cell RNA sequencing to bone marrow(BM) samples from patients with(n=20) and without(n=12) MRD after allogeneic hematopoietic stem cell transplantation. A comprehensive immune landscape with 184,231 cells was created. Compared with CD8+T cells enriched in the MRDnegative group(MRD-＿CD8), those enriched in the MRD-positive group(MRD+＿CD8) showed lower expression levels of cytotoxicity-related genes. Three monocyte clusters(i.e., MRD+＿M) and three B-cell clusters(i.e., MRD+＿B) were enriched in the MRD-positive group. Conversion from an MRD-positive state to an MRD-negative state was accompanied by an increase in MRD-＿CD8 clusters and vice versa. MRDenriched cell clusters employed the macrophage migration inhibitory factor pathway to regulate MRD-＿CD8 clusters. These findings revealed the characteristics of the immune cell landscape in MRD positivity, which will allow for a better understanding of the immune mechanisms for MRD conversion.

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Vault RNAs(vtRNAs):Rediscovered non-coding RNAs with diverse physiological and pathological activities

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Genes & Diseases 2024年第2期11卷 772-787页

作者： Mahsa Aghajani Mir Deputy of research and Technology Health Research InstituteBabol University of Medical SciencesBabol 47176-4774Iran

The physicochemical characteristics of RNA admit non-coding RNAs to perform a different range of biological acts through various mechanisms and are involved in regulating a diversity of fundamental ***,some reports of pathological conditions have proved abnormal expression of many non-coding RNAs guides the *** RNAs are a class of non-coding RNAs containing stem regions or loops with well-conserved sequence patterns that play a fundamental role in the function of vault particles through RNA-ligand,RNA–RNA,or RNA-protein *** together,vault RNAs have been proposed to be involved in a variety of functions such as cell proliferation,nucleocytoplasmic transport,intracellular detoxification processes,multidrug resistance,apoptosis,and autophagy,and serve as microRNA precursors and signaling *** decades of investigations devoted,the biological function of the vault particle or the vault RNAs is not yet completely *** this review,the current scientific assertions of the vital vault RNAs functions were discussed.

关键词： ncRNA Vault complex Vault RNA vtRNA viral infection tumorigenesis

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Enhancing immunotherapy efficacy against MHC-I deficient triple-negative breast cancer using LCL161-loaded macrophage membranedecorated nanoparticles

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3218-3231页

作者： Wen Zhang Yihui Zhai Ying Cai Xiang Gong Yunxuan Jiang Rong Rong Chao Zheng Binyu Zhu Helen He Zhu Hao Wang Yaping Li Pengcheng Zhang China State institute of Pharmaceutical Industry Shanghai 201203China State Key Laboratory of Drug research&Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Biomedical Engineering&State Key Laboratory of Advanced Medical Materials and Devices ShanghaiTech UniversityShanghai 201210China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China Yantai institute of Materia Medica Shandong 264000China State Key Laboratory of Oncogenes and Related Genes Renji-Med-X Stem Cell Research CenterDepartment of UrologyRen Ji HospitalSchool of Medicine and School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200127China University of Chinese Academy of Sciences Beijing 100049China

Current cytotoxic T lymphocyte(CTL)activating immunotherapy requires a major histocompatibility complex I(MHC-I)-mediated presentation of tumor-associated antigens,which malfunctions in around half of patients with triple-negative breast cancer(TNBC).Here,we create a LCL161-loaded macrophage membrane decorated nanoparticle(LMN)for immunotherapy of MHC-I-deficient *** on the macrophage membrane helps LMNs recognize CD47-expressing cancer cells for targeted delivery of LCL161,which induces the release of high mobility group protein 1 and proinflammatory cytokines from cancer *** released cytokines and high mobility group protein 1 activate antitumor immunity by increasing the intratumoral density of the phagocytic macrophage subtype by 15 times and elevating the intratumoral concentration of CTL lymphotoxin by 4.6 *** also block CD47-mediated phagocytosis *** inhibit the growth of MHC-I-deficient TNBC tumors,as well as those resistant to combined therapy of anti-PDL1 antibody and albumin-bound paclitaxel,and prolong the survival of animals,during which process CTLs also play important *** macrophage membrane-decorated nanoparticle presents a generalizable platform for increasing macrophagemediated antitumor immunity for effective immunotherapy of MHC-I-deficient cancers.

关键词： MHC-I deficiency Macrophage CD47 Immunotherapy Triple-negative breast cancer Phagocytosis Immune checkpoint Innate immunity

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The Effect of Spironolactone Loading on the Properties of 3D-Printed Polycaprolactone/Gold Nanoparticles Composite Scaffolds for Myocardial Tissue Engineering

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Journal of Bionic Engineering 2024年第2期21卷 924-937页

作者： Sharareh Ghaziof Shahrokh Shojaei Mehdi Mehdikhani Mohammad Khodaei Milad Jafari Nodoushan Department of Biomedical Engineering Central Tehran BranchIslamic Azad UniversityTehran***Iran stem cells research Center Tissue Engineering and Regenerative Medicine InstituteCentral Tehran BranchIslamic Azad UniversityTehran***Iran Department of Biomedical Engineering Faculty of EngineeringUniversity of IsfahanIsfahan***Iran Materials Engineering Group Golpayegan College of EngineeringIsfahan University of TechnologyGolpayegan87717-67498Iran Hard Tissue Engineering research Center Tissue Engineering and Regenerative Medicine InstituteCentral Tehran BranchIslamic Azad UniversityTehran***Iran

Engineered cardiac constructs(ECC)aid in the progression of regenerative medicine,disease modeling and targeted drug delivery to adjust and aim the release of remedial combination as well as decrease the side effects of *** this research,polycaprolactone/gold nanoparticles(PCL/GNPs)three-dimensional(3D)composite scaffolds were manufactured by 3D printing using the fused deposition modeling(FDM)method and then coated with gelatin/spironolactone(GEL/SPL).Scanning electron microscopy(SEM)and Fourier transform-infrared spectroscopy(FTIR–ATR)were applied to characterize the ***,drug release,biodegradation,behavior of the myoblasts(H9C2)cell line,and cytotoxicity of the 3D scaffolds were *** microstructural observation of the scaffolds reported interconnected pores with 150–300µm in *** 3D scaffolds were degraded significantly after 28 days of immersion in stimulated body fluid(SBF),with the maximum rate of GEL-coated 3D *** release from cross-linked GEL coating demonstrated the excess of drug release over time,and according to the control release systems,the drug delivery systems(DDS)went into balance after the 14th *** addition,cell culture study showed that with the addition of GNPs,the proliferation of(H9C2)was enhanced,and with GEL/SPL coating the cell attachment and viability were improved *** findings suggested that PCL/GNPs 3D scaffolds coated with GEL/SPL can be an appropriate choice for myocardial tissue engineering.

关键词： Polycaprolactone Gold nanoparticles Drug delivery systems Spironolactone cell behavior Myoblasts

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Game-changing insights on vertebral skeletal stem cells in bone metastasis and therapeutic horizons

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Oncology research 2024年第1期32卷 95-98页

作者： QIUQIANG CHEN XIAOLEI ZHAO WENXUE MA Key Laboratory for Translational Medicine The First Affiliated HospitalHuzhou University School of MedicineHuzhou313000China Department of Urology Huaihe Hospital of Henan UniversityKaifeng475004China Department of Medicine Moores Cancer CenterSanford Stem Cell InstituteUniversity of California San DiegoLa Jolla92093USA

Greenblatt and his team have unveiled vertebral skeletal stem cells(vSSCs)as a critical player in the landscape of bone *** commentary delves into the transformative discoveries surrounding vSSCs,emphasizing their distinct role in bone metastasis compared to other stem cell *** illuminate the unique properties and functions of vSSCs,which may account for the elevated susceptibility of vertebral bones to metastatic ***,we explore the exciting therapeutic horizons opened by this newfound *** include potential interventions targeting vSSCs,modulation of associated signaling pathways,and broader implications for the treatment and management of bone *** shedding light on these game-changing insights,we hope to pave the way for novel strategies that could revolutionize the prognosis and treatment landscape for cancer patients with metastatic bone disease.

关键词： Vertebral skeletal stem cells(vSSCs) stem cell research Metastasis Breast prostate and lung cancers Spinal metastasis Matthew Greenblatt Genetic expressions

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IRE1α regulates the PTHrP-IHH feedback loop to orchestrate chondrocyte hypertrophy and cartilage mineralization

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Genes & Diseases 2024年第1期11卷 464-478页

作者： Mengtian Fan Nana Geng Xingyue Li Danyang Yin Yuyou Yang Rong Jiang Cheng Chen Naibo Feng Li Liang Xiaoli Li Fengtao Luo Huabing Qi Qiaoyan Tan Yangli Xie Fengjin Guo Laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical ScienceChongqing Medical UniversityChongqing 400016China Laboratory of stem cells and Tissue Engineering School of Basic Medical ScienceChongqing Medical UniversityChongqing 400016China Department of Orthopedics The 1st Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Wound Repair and Rehabilitation Medicine State Key Laboratory of TraumaBurns and Combined InjuryTrauma CenterResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China

Cartilage development is controlled by the highly synergistic proliferation and differentiation of growth plate chondrocytes,in which the Indian hedgehog(IHH)and parathyroid hormone-related protein-parathyroid hormone-1 receptor(PTHrP-PTH1R)feedback loop is *** inositol-requiring enzyme 1a/X-box-binding protein-1 spliced(IRE1α/XBP1s)branch of the unfolded protein response(UPR)is essential for normal cartilage ***,the precise role of ER stress effector IRE1α,encoded by endoplasmic reticulum to nucleus signaling 1(ERN1),in skeletal development remains ***,we reported that loss of IRE1α accelerates chondrocyte hypertrophy and promotes endochondral bone ***1 acts as a negative regulator of chondrocyte proliferation and differentiation in postnatal growth *** deficiency interrupted PTHrP/PTH1R and IHH homeostasis leading to impaired chondrocyte hypertrophy and ***1s,produced by p-IRE1α-mediated splicing,binds and up-regulates PTH1R and IHH,which coordinate cartilage ***,ER stress cannot be activated normally in ERN1-deficient *** conclusion,ERN1 deficiency accelerates chondrocyte hypertrophy and cartilage mineralization by impairing the homeostasis of the IHH and PTHrP/PTH1R feedback loop and ER ***1 may have a potential role as a new target for cartilage growth and maturation.

关键词： Cartilage development ER stress ERN1 IHH PTHrP/PTH1R

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