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基因与疾病（英文）
基因与疾病（英文）
基因与疾病（英文）/Journal Genes & DiseasesCSCD
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    The journey towards physiology and pathology:Tracing the path of neuregulin 4

    Min ChenJieying ZhuHongyang LuoWangjing Mu...
    687-700页
    查看更多>>摘要：Neuregulin 4(Nrg4),an epidermal growth factor(EGF)family member,can bind to and activate the ErbB4 receptor tyrosine kinase.Nrg4 has five different isoforms by alternative splicing and performs a wide variety of functions.Nrg4 is involved in a spectrum of physiolog-ical processes including neurobiogenesis,lipid metabolism,glucose metabolism,thermogene-sis,and angiogenesis.In pathological processes,Nrg4 inhibits inflammatory factor levels and suppresses apoptosis in inflammatory diseases.In addition,Nrg4 could ameliorate obesity,in-sulin resistance,and cardiovascular diseases.Furthermore,Nrg4 improves non-alcoholic fatty liver disease(NAFLD)by promoting autophagy,improving lipid metabolism,and inhibiting cell death of hepatocytes.Besides,Nrg4 is closely related to the development of cancer,hyperthy-roidism,and some other diseases.Therefore,elucidation of the functional role and mecha-nisms of Nrg4 will provide a clearer view of the therapeutic potential and possible risks of Nrg4.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    The Wnt-dependent and Wnt-independent functions of BCL9 in development,tumorigenesis,and immunity:Implications in therapeutic opportunities

    Minjie WuHeng DongChao XuMengqing Sun...
    701-710页
    查看更多>>摘要：B-cell CLL/lymphoma 9(BCL9)is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types,mainly through potentiating the Wnt/β-catenin signaling.However,increasing evidences indicate that BCL9 also plays multiple Wnt-independent roles.Herein,we summarized the updates of the canonical and non-canon-ical functions of BCL9 in cellular,physiological,or pathological processes.Moreover,we also concluded that the targeted inhibitors disrupt the interaction of β-catenin with BCL9 reported recently.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Decoding m6A mRNA methylation by reader proteins in liver diseases

    Lijiao SunXin ChenSai ZhuJianan Wang...
    711-726页
    查看更多>>摘要：N6-methyladenosine(m6A)is a dynamic and reversible epigenetic regulation.As the most prevalent internal post-transcriptional modification in eukaryotic RNA,it participates in the regulation of gene expression through various mechanisms,such as mRNA splicing,nu-clear export,localization,translation efficiency,mRNA stability,and structural transforma-tion.The involvement of m6A in the regulation of gene expression depends on the specific recognition of m6A-modified RNA by reader proteins.In the pathogenesis and treatment of liver disease,studies have found that the expression levels of key genes that promote or inhibit the development of liver disease are regulated by m6A modification,in which abnormal expres-sion of reader proteins determines the fate of these gene transcripts.In this review,we intro-duce m6A readers,summarize the recognition and regulatory mechanisms of m6A readers on mRNA,and focus on the biological functions and mechanisms of m6A readers in liver cancer,viral hepatitis,non-alcoholic fatty liver disease(NAFLD),hepatic fibrosis(HF),acute liver injury(ALI),and other liver diseases.This information is expected to be of high value to re-searchers deciphering the links between m6A readers and human liver diseases.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    WNT/β-catenin signaling in hepatocellular carcinoma:The aberrant activation,pathogenic roles,and therapeutic opportunities

    Anna Gajos-MichniewiczMalgorzata Czyz
    727-746页
    查看更多>>摘要：Hepatocellular carcinoma(HCC)is a liver cancer,highly heterogeneous both at the histopathological and molecular levels.It arises from hepatocytes as the result of the accumu-lation of numerous genomic alterations in various signaling pathways,including canonical WNT/β-catenin,AKT/mTOR,MAPK pathways as well as signaling associated with telomere maintenance,p53/cell cycle regulation,epigenetic modifiers,and oxidative stress.The role of WNT/β-catenin signaling in liver homeostasis and regeneration is well established,whereas in development and progression of HCC is extensively studied.Herein,we review recent ad-vances in our understanding of how WNT/β-catenin signaling facilitates the HCC development,acquisition of stemness features,metastasis,and resistance to treatment.We outline genetic and epigenetic alterations that lead to activated WNT/β-catenin signaling in HCC.We discuss the pivotal roles of CTNNB1 mutations,aberrantly expressed non-coding RNAs and complexity of crosstalk between WNT/β-catenin signaling and other signaling pathways as challenging or advantageous aspects of therapy development and molecular stratification of HCC patients for treatment.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Cardiac regeneration:Pre-existing cardiomyocyte as the hub of novel signaling pathway

    Tao WangXinzhe ChenKai WangJie Ju...
    747-759页
    查看更多>>摘要：In the mammalian heart,cardiomyocytes are forced to withdraw from the cell cy-cle shortly after birth,limiting the ability of the heart to regenerate and repair.The develop-ment of multimodal regulation of cardiac proliferation has verified that pre-existing cardiomyocyte proliferation is an essential driver of cardiac renewal.With the continuous development of genetic lineage tracking technology,it has been revealed that cell cycle activ-ity produces polyploid cardiomyocytes during the embryonic,juvenile,and adult stages of car-diogenesis,but newly formed mononucleated diploid cardiomyocytes also elevated sporadically during myocardial infarction.It implied that adult cardiomyocytes have a weak regenerative capacity under the condition of ischemia injury,which offers hope for the clinical treatment of myocardial infarction.However,the regeneration frequency and source of cardi-omyocytes are still low,and the mechanism of regulating cardiomyocyte proliferation remains further explained.It is noteworthy to explore what force triggers endogenous cardiomyocyte proliferation and heart regeneration.Here,we focused on summarizing the recent research progress of emerging endogenous key modulators and crosstalk with other signaling pathways and furnished valuable insights into the internal mechanism of heart regeneration.In addition,myocardial transcription factors,non-coding RNAs,cyclins,and cell cycle-dependent kinases are involved in the multimodal regulation of pre-existing cardiomyocyte proliferation.Ulti-mately,awakening the myocardial proliferation endogenous modulator and regeneration path-ways may be the final battlefield for the regenerative therapy of cardiovascular diseases.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Hippo-YAP/TAZ signaling in breast cancer:Reciprocal regulation of microRNAs and implications in precision medicine

    Farzad SadriSeyede fatemeh HosseiniZohreh RezaeiMohammad Fereidouni...
    760-771页
    查看更多>>摘要：Breast cancer is a molecularly heterogeneous disease and the most common female malignancy.In recent years,therapy approaches have evolved to accommodate molecular di-versity,with a focus on more biologically based therapies to minimize negative consequences.To regulate cell fate in human breast cells,the Hippo signaling pathway has been associated with the alpha subtype of estrogen receptors.This pathway regulates tissue size,regenera-tion,and healing,as well as the survival of tissue-specific stem cells,proliferation,and apoptosis in a variety of organs,allowing for cell differentiation.Hippo signaling is mediated by the kinases MST1,MST2,LATS1,and LATS2,as well as the adaptor proteins SAV1 and MOB.These kinases phosphorylate the downstream effectors of the Hippo pathway,yes-associated protein(YAP),and transcriptional coactivator with PDZ-binding motif(TAZ),suppressing the expression of their downstream target genes.The Hippo signaling pathway kinase cascade plays a significant role in all cancers.Understanding the principles of this kinase cascade would prevent the occurrence of breast cancer.In recent years,small noncoding RNAs,or microRNAs,have been implicated in the development of several malignancies,including breast cancer.The interconnections between miRNAs and Hippo signaling pathway core proteins in the breast,on the other hand,remain poorly understood.In this review,we focused on high-lighting the Hippo signaling system,its key parts,its importance in breast cancer,and its regu-lation by miRNAs and other related pathways.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

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

    Mahsa Aghajani Mir
    772-787页
    查看更多>>摘要：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 processes.Notably,some reports of pathological conditions have proved abnormal expression of many non-coding RNAs guides the ailment.Vault RNAs are a class of non-coding RNAs containing stem regions or loops with well-conserved sequence pat-terns that play a fundamental role in the function of vault particles through RNA-ligand,RNA-RNA,or RNA-protein interactions.Taken together,vault RNAs have been proposed to be involved in a variety of functions such as cell proliferation,nucleocytoplasmic transport,intra-cellular detoxification processes,multidrug resistance,apoptosis,and autophagy,and serve as microRNA precursors and signaling pathways.Despite decades of investigations devoted,the biological function of the vault particle or the vault RNAs is not yet completely cleared.In this review,the current scientific assertions of the vital vault RNAs functions were discussed.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    RSPO2 as Wnt signaling enabler:Important roles in cancer development and therapeutic opportunities

    Ankit SrivastavaDeeksha RikhariSameer Srivastava
    788-806页
    查看更多>>摘要：R-spondins are secretory proteins localized in the endoplasmic reticulum and Golgi bodies and are processed through the secretory pathway.Among the R-spondin family,RSPO2 has emanated as a novel regulator of Wnt signaling,which has now been acknowledged in numerous in vitro and in vivo studies.Cancer is an abnormal growth of cells that proliferates and spreads uncontrollably due to the accumulation of genetic and epigenetic factors that constitutively activate Wnt signaling in various types of cancer.Colorectal cancer(CRC)begins when cells in the colon and rectum follow an indefinite pattern of division due to aberrant Wnt activation as one of the key hallmarks.Decades-long progress in research on R-spondins has demonstrated their oncogenic function in distinct cancer types,particularly CRC.As a critical regulator of the Wnt pathway,it modulates several phenotypes of cells,such as cell prolifer-ation,invasion,migration,and cancer stem cell properties.Recently,RSPO mutations,gene rearrangements,fusions,copy number alterations,and altered gene expression have also been identified in a variety of cancers,including CRC.In this review,we addressed the recent up-dates regarding the recurrently altered R-spondins with special emphasis on the RSPO2 gene and its involvement in potentiating Wnt signaling in CRC.In addition to the compelling physi-ological and biological roles in cellular fate and regulation,we propose that RSPO2 would be valuable as a potential biomarker for prognostic,diagnostic,and therapeutic use in CRC.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Immune checkpoint inhibitors break whose heart?Perspectives from cardio-immuno-oncology

    Yingying HeHui YuShuang DaiMiao He...
    807-818页
    查看更多>>摘要：Immune checkpoint inhibitors(ICIs)are monoclonal antibody antagonists,which can block cytotoxic T lymphocyte antigen-4(CTLA-4),programmed death-1/ligand-1(PD-1/PD-L1)pathways,and other molecules exploited by tumor cells to evade T cell-mediated im-mune response.ICIs have transformed the treatment landscape for various cancers due to their amazing efficacy.Many anti-tumor therapies,including targeted therapy,radiotherapy,and chemotherapy,combine ICIs to make the treatment more effective.However,the off-target immune activation caused by ICIs may lead to a broad spectrum of immune-related adverse events(irAEs)affecting multiple organ systems.Among irAEs,cardiotoxicity induced by ICIs,uncommon but fatal,has greatly offset survival benefits from ICIs,which is heartbreaking for both patients and clinicians.Consequently,such cardiotoxicity requires special vigilance,and it has become a common challenge both for patients and clinicians.This article reviewed the clinical manifestations and influence of cardiotoxicity from the view of patients and clini-cians,elaborated on the underlying mechanisms in conjunction with animal studies,and then attempted to propose management strategies from a cardio-immuno-oncology multidisci-plinary perspective.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Fantastic voyage:The journey of NLRP3 inflammasome activation

    Xiangyong QueSihao ZhengQibin SongHuadong Pei...
    819-829页
    查看更多>>摘要：NLRP3 inflammasome,an intracellular multiprotein complex,can be activated by a range of pathogenic microbes or endogenous hazardous chemicals.Its activation results in the release of cytokines such as IL-1 β and IL-18,as well as Gasdermin D which eventually causes pyroptosis.The activation of NLRP3 inflammasome is under strict control and regu-lation by numerous pathways and mechanisms.Its excessive activation can lead to a persis-tent inflammatory response,which is linked to the onset and progression of severe illnesses.Recent studies have revealed that the subcellular localization of NLRP3 changes significantly during the activation process.In this review,we review the current understanding of the molecular mechanism of NLRP3 inflammasome activation,focusing on the subcellular local-ization of NLRP3 and the associated regulatory mechanisms.We aim to provide a compre-hensive understanding of the dynamic transportation,activation,and degradation processes of NLRP3.
      原文链接:
    • NETL
    • NSTL
    • 万方数据