• MinireviewFebruary 29, 2020

    0 426 823

    Abstract : Comprehensive inhibition of RUNX1, RUNX2, and RUNX3 led to marked cell suppression compared with inhibition of RUNX1 alone, clarifying that the RUNX family members are important for proliferation and maintenance of diverse cancers, and “cluster regulation of RUNX (CROX)” is a very effective strategy to suppress cancer cells. Recent studies reported by us and other groups suggested that wild-type RUNX1 is needed for survival and proliferation of certain types of leukemia, lung cancer, gastric cancer, etc. and for their one of metastatic target sites such as born marrow endothelial niche, suggesting that RUNX1 often functions oncogenic manners in cancer cells. In this review, we describe the significance and paradoxical requirement of RUNX1 tumor suppressor in leukemia and even solid cancers based on recent our findings such as “genetic compensation of RUNX family transcription factors (the compensation mechanism for the total level of RUNX family protein expression)”, “RUNX1 inhibition-induced inhibitory effects on leukemia cells and on solid cancers through p53 activation”, and “autonomous feedback loop of RUNX1-p53-CBFB in acute myeloid leukemia cells”. Taken together, these findings identify a crucial role for the RUNX cluster in the maintenance and progression of cancers and suggest that modulation of the RUNX cluster using the pyrrole-imidazole polyamide gene-switch technology is a potential novel therapeutic approach to control cancers.

  • MinireviewJanuary 31, 2020

    0 552 1314

    Lung Cancer Staging and Associated Genetic and Epigenetic Events

    Dohun Kim, You-Soub Lee, Duk-Hwan Kim, and Suk-Chul Bae

    Mol. Cells 2020; 43(1): 1-9

    Abstract : The first step in treating lung cancer is to establish the stage of the disease, which in turn determines the treatment options and prognosis of the patient. Many factors are involved in lung cancer staging, but all involve anatomical information. However, new approaches, mainly those based on the molecular biology of cancer, have recently changed the paradigm for lung cancer treatment and have not yet been incorporated into staging. In a group of patients of the same stage who receive the same treatment, some may experience unexpected recurrence or metastasis, largely because current staging methods do not reflect the findings of molecular biological studies. In this review, we provide a brief summary of the latest research on lung cancer staging and the molecular events associated with carcinogenesis. We hope that this paper will serve as a bridge between clinicians and basic researchers and aid in our understanding of lung cancer.

  • MinireviewJanuary 31, 2020

    0 848 1634

    Mitophagy and Innate Immunity in Infection

    Dong-Hyung Cho, Jin Kyung Kim, and Eun-Kyeong Jo

    Mol. Cells 2020; 43(1): 10-22

    Abstract : Mitochondria have several quality control mechanisms by which they maintain cellular homeostasis and ensure that the molecular machinery is protected from stress. Mitophagy, selective autophagy of mitochondria, promotes mitochondrial quality control by inducing clearance of damaged mitochondria via the autophagic machinery. Accumulating evidence suggests that mitophagy is modulated by various microbial components in an attempt to affect the innate immune response to infection. In addition, mitophagy plays a key role in the regulation of inflammatory signaling, and mitochondrial danger signals such as mitochondrial DNA translocated into the cytosol can lead to exaggerated inflammatory responses. In this review, we present current knowledge on the functional aspects of mitophagy and its crosstalk with innate immune signaling during infection. A deeper understanding of the role of mitophagy could facilitate the development of more effective therapeutic strategies against various infections.

  • MinireviewDecember 31, 2019

    0 1326 3487

    Abstract : Aging is the most important single risk factor for many chronic diseases such as cancer, metabolic syndrome, and neurodegenerative disorders. Targeting aging itself might, therefore, be a better strategy than targeting each chronic disease individually for enhancing human health. Although much should be achieved for completely understanding the biological basis of aging, cellular senescence is now believed to mainly contribute to organismal aging via two independent, yet not mutually exclusive mechanisms: on the one hand, senescence of stem cells leads to exhaustion of stem cells and thus decreases tissue regeneration. On the other hand, senescent cells secrete many proinflammatory cytokines, chemokines, growth factors, and proteases, collectively termed as the senescence-associated secretory phenotype (SASP), which causes chronic inflammation and tissue dysfunction. Much effort has been recently made to therapeutically target detrimental effects of cellular senescence including selectively eliminating senescent cells (senolytics) and modulating a proinflammatory senescent secretome (senostatics). Here, we discuss current progress and limitations in understanding molecular mechanisms of senolytics and senostatics and therapeutic strategies for applying them. Furthermore, we propose how these novel interventions for aging treatment could be improved, based on lessons learned from cancer treatment.

  • MinireviewDecember 31, 2019

    0 632 1481

    Abstract : PIWI Argonaute proteins and Piwi-interacting RNAs (piRNAs) are expressed in all animal species and play a critical role in cellular defense by inhibiting the activation of transposable elements in the germline. Recently, new evidence suggests that PIWI proteins and piRNAs also play important roles in various somatic tissues, including neurons. This review summarizes the neuronal functions of the PIWI-piRNA pathway in multiple animal species, including their involvement in axon regeneration, behavior, memory formation, and transgenerational epigenetic inheritance of adaptive memory. This review also discusses the consequences of dysregulation of neuronal PIWI-piRNA pathways in certain neurological disorders, including neurodevelopmental and neurodegenerative diseases. A full understanding of neuronal PIWI-piRNA pathways will ultimately provide novel insights into small RNA biology and could potentially provide precise targets for therapeutic applications.

  • MinireviewNovember 30, 2019

    0 1351 2508

    Abstract : Significant knowledge about the pathophysiology of Alzheimer’s disease (AD) has been gained in the last century; however, the understanding of its causes of onset remains limited. Late-onset AD is observed in about 95% of patients, and APOE4-encoding apolipoprotein E4 (ApoE4) is strongly associated with these cases. As an apolipoprotein, the function of ApoE in brain cholesterol transport has been extensively studied and widely appreciated. Development of new technologies such as human-induced pluripotent stem cells (hiPSCs) and CRISPR-Cas9 genome editing tools have enabled us to develop human brain model systems in vitro and readily manipulate genomic information. In the context of these advances, recent studies provide strong evidence that abnormal cholesterol metabolism by ApoE4 could be linked to AD-associated pathology. In this review, we discuss novel discoveries in brain cholesterol dysregulation by ApoE4. We further elaborate cell type-specific roles in cholesterol regulation of four major brain cell types, neurons, astrocytes, microglia, and oligodendrocytes, and how its dysregulation can be linked to AD pathology.

  • MinireviewNovember 30, 2019

    0 1262 2499

    Cellular and Molecular Links between Autoimmunity and Lipid Metabolism

    Heeju Ryu, Jiyeon Kim, Daehong Kim, Jeong-Eun Lee, and Yeonseok Chung

    Mol. Cells 2019; 42(11): 747-754

    Abstract : The incidence of atherosclerosis is higher among patients with several autoimmune diseases such as psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It is well documented that innate immune cells including macrophages and dendritic cells sense lipid species such as saturated fatty acids and oxidized low-density lipoprotein and produce pro-inflammatory cytokines and chemokines. However, whether a hyperlipidemic environment also impacts autoimmune T cell responses has been unclear. Among CD4+ T cells, Th17 and follicular helper T (Tfh) cells are known to play pathogenic roles in the development of hyperlipidemia-associated autoimmune diseases. This review gives an overview of the cellular and molecular mechanisms by which dysregulated lipid metabolism impacts the pathogenesis of autoimmune diseases, with specific emphasis on Th17 and Tfh cells.

  • MinireviewOctober 31, 2019

    0 484 1478

    Abstract : Transfer RNA-derived small RNAs (tsRNAs) play a role in various cellular processes. Accumulating evidence has revealed that tsRNAs are deeply implicated in human diseases, such as various cancers and neurological disorders, suggesting that tsRNAs should be investigated to develop novel therapeutic intervention. tsRNAs provide more complexity to the physiological role of transfer RNAs by repressing or activating protein synthesis with distinct mechanisms. Here, we highlight the detailed mechanism of tsRNA-mediated dual regulation in protein synthesis and discuss the necessity of novel sequencing technology to learn more about tsRNAs.

  • MinireviewSeptember 30, 2019

    0 1637 4113

    Past, Present, and Future of Brain Organoid Technology

    Bonsang Koo, Baekgyu Choi, Hoewon Park, and Ki-Jun Yoon

    Mol. Cells 2019; 42(9): 617-627

    Abstract : Brain organoids are an exciting new technology with the potential to significantly change our understanding of the development and disorders of the human brain. With step-by-step differentiation protocols, three-dimensional neural tissues are self-organized from pluripotent stem cells, and recapitulate the major millstones of human brain development in vitro. Recent studies have shown that brain organoids can mimic the spatiotemporal dynamicity of neurogenesis, the formation of regional neural circuitry, and the integration of glial cells into a neural network. This suggests that brain organoids could serve as a representative model system to study the human brain. In this review, we will overview the development of brain organoid technology, its current progress and applications, and future prospects of this technology.

  • MinireviewAugust 31, 2019

    0 478 1617

    Transient Receptor Potential Channels and Metabolism

    Subash Dhakal and Youngseok Lee

    Mol. Cells 2019; 42(8): 569-578

    Abstract : Transient receptor potential (TRP) channels are nonselective cationic channels, conserved among flies to humans. Most TRP channels have well known functions in chemosensation, thermosensation, and mechanosensation. In addition to being sensing environmental changes, many TRP channels are also internal sensors that help maintain homeostasis. Recent improvements to analytical methods for genomics and metabolomics allow us to investigate these channels in both mutant animals and humans. In this review, we discuss three aspects of TRP channels, which are their role in metabolism, their functional characteristics, and their role in metabolic syndrome. First, we introduce each TRP channel superfamily and their particular roles in metabolism. Second, we provide evidence for which metabolites TRP channels affect, such as lipids or glucose. Third, we discuss correlations between TRP channels and obesity, diabetes, and mucolipidosis. The cellular metabolism of TRP channels gives us possible therapeutic approaches for an effective prophylaxis of metabolic syndromes.

  • MinireviewJuly 31, 2019

    0 715 2376

    Role of RIN4 in Regulating PAMP-Triggered Immunity and Effector-Triggered Immunity: Current Status and Future Perspectives

    Sujit Kumar Ray , Donah Mary Macoy , Woe-Yeon Kim , Sang Yeol Lee , and Min Gab Kim

    Mol. Cells 2019; 42(7): 503-511

    Abstract : As sessile organisms, plants have developed sophisticated system to defend themselves against microbial attack. Since plants do not have specialized immune cells, all plant cells appear to have the innate ability to recognize pathogens and turn on an appropriate defense response. The plant innate immune system has two major branches: PAMPs (pathogen associated molecular patterns)-triggered immunity (PTI) and effector-triggered immunity (ETI). The ability to discriminate between self and non-self is a fundamental feature of living organisms, and it is a prerequisite for the activation of plant defenses specific to microbial infection. Arabidopsis cells express receptors that detect extracellular molecules or structures of the microbes, which are called collectively PAMPs and activate PTI. However, nucleotide-binding site leucine-rich repeats (NB-LRR) proteins mediated ETI is induced by direct or indirect recognition of effector molecules encoded by avr genes. In Arabidopsis, plasma-membrane localized multifunctional protein RIN4 (RPM1-interacting protein 4) plays important role in both PTI and ETI. Previous studies have suggested that RIN4 functions as a negative regulator of PTI. In addition, many different bacterial effector proteins modify RIN4 to destabilize plant immunity and several NB-LRR proteins, including RPM1 (resistance to Pseudomonas syringae pv. maculicola 1), RPS2 (resistance to P. syringae 2) guard RIN4. This review summarizes the current studies that have described signaling mechanism of RIN4 function, modification of RIN4 by bacterial effectors and different interacting partner of RIN4 in defense related pathway. In addition, the emerging role of the RIN4 in plant physiology and intercellular signaling as it presents in exosomes will be discussed.

  • MinireviewJuly 31, 2019

    0 365 1697

    Abstract : Chromosomes located in the nucleus form discrete units of genetic material composed of DNA and protein complexes. The genetic information is encoded in linear DNA sequences, but its interpretation requires an understanding of three-dimensional (3D) structure of the chromosome, in which distant DNA sequences can be juxtaposed by highly condensed chromatin packing in the space of nucleus to precisely control gene expression. Recent technological innovations in exploring higher-order chromatin structure have uncovered organizational principles of the 3D genome and its various biological implications. Very recently, it has been reported that large-scale genomic variations may disrupt higher-order chromatin organization and as a consequence, greatly contribute to disease-specific gene regulation for a range of human diseases. Here, we review recent developments in studying the effect of structural variation in gene regulation, and the detection and the interpretation of structural variations in the context of 3D chromatin structure.

Mol. Cells
Jul 31, 2022 Vol.45 No.7, pp. 435~512
Mesenchymal stem cells (MSCs) are multipotent stem cells capable of differentiating into mesodermal lineages like adipogenic, osteogenic, and chondrogenic. Alcian blue-positive extracellular matrix secreted by chondrocytes in the lacuna confirmed the chondrogenic differentiation of MSCs (Bashyal et al., pp. 479-494).

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