journal
https://read.qxmd.com/read/38531964/extracellular-vesicle-mediated-transfer-of-mirna-1-from-primary-tumors-represses-the-growth-of-distant-metastases
#1
JOURNAL ARTICLE
Chae-Yi Kim, Kang-Hoon Lee, Keun Hong Son, Tae-Jin Shin, Je-Yoel Cho
Metastases originate from primary tumors and reach distant organs. Growing evidence suggests that metastases are under the control of primary tumors even outside the primary site; however, the mechanisms by which primary tumors remotely control metastases remain unclear. Here, we discovered a molecular mechanism by which primary tumors suppress metastatic growth. Interestingly, we found that extracellular vesicles (EVs) derived from the primary tumor can inhibit the growth of metastases both in vitro and in vivo...
March 27, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38531963/involvement-of-dj-1-in-the-pathogenesis-of-intervertebral-disc-degeneration-via-hexokinase-2-mediated-mitophagy
#2
JOURNAL ARTICLE
Jialiang Lin, Longjie Wang, Yuhao Wu, Qian Xiang, Yongzhao Zhao, Xuanqi Zheng, Shuai Jiang, Zhuoran Sun, Dongwei Fan, Weishi Li
Intervertebral disc degeneration (IDD) is an important pathological basis for degenerative spinal diseases and is involved in mitophagy dysfunction. However, the molecular mechanisms underlying mitophagy regulation in IDD remain unclear. This study aimed to clarify the role of DJ-1 in regulating mitophagy during IDD pathogenesis. Here, we showed that the mitochondrial localization of DJ-1 in nucleus pulposus cells (NPCs) first increased and then decreased in response to oxidative stress. Subsequently, loss- and gain-of-function experiments revealed that overexpression of DJ-1 in NPCs inhibited oxidative stress-induced mitochondrial dysfunction and mitochondria-dependent apoptosis, whereas knockdown of DJ-1 had the opposite effect...
March 27, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38528124/acetyl-coa-synthetase-2-contributes-to-a-better-prognosis-for-liver-cancer-by-switching-acetate-glucose-metabolism
#3
JOURNAL ARTICLE
Kyung Hee Jung, Sujin Lee, Han Sun Kim, Jin-Mo Kim, Yun Ji Lee, Min Seok Park, Myeong-Seong Seo, Misu Lee, Mijin Yun, Sunghyouk Park, Soon-Sun Hong
Acetyl-CoA synthetase 2 (ACSS2)-dependent acetate usage has generally been associated with tumorigenesis and increased malignancy in cancers under nutrient-depleted conditions. However, the nutrient usage and metabolic characteristics of the liver differ from those of other organs; therefore, the mechanism of ACSS2-mediated acetate metabolism may also differ in liver cancer. To elucidate the underlying mechanisms of ACSS2 in liver cancer and acetate metabolism, the relationships between patient acetate uptake and metabolic characteristics and between ACSS2 and tumor malignancies were comprehensively studied in vitro, in vivo and in humans...
March 25, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38486106/cancer-derived-exosomal-alu-rna-promotes-colorectal-cancer-progression
#4
JOURNAL ARTICLE
Sara Magliacane Trotta, Antonio Adinolfi, Luca D'Orsi, Sonia Panico, Grazia Mercadante, Patrick Mehlen, Jayakrishna Ambati, Sandro De Falco, Valeria Tarallo
Inflammation plays a crucial role in cancer progression, but the relevance of the inflammasome remains unclear. Alu RNA was the first endogenous nucleic acid shown to activate the NLRP3 (nucleotide-binding domain leucine-rich repeat containing 3) inflammasome. Here, we showed that Alu RNA can induce epithelial-to-mesenchymal transition (EMT) through NLRP3 inflammasome activation and IL-1β release in colorectal cancer (CRC) cells. Alu RNA is stored, transported and transferred to CRC cells by exosomes...
March 14, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38486105/prmt7-regulates-the-jak-stat-socs3-signaling-pathway-in-postmenopausal-cardiomyopathy
#5
JOURNAL ARTICLE
Byeong-Yun Ahn, Yan Zhang, Shibo Wei, Yideul Jeong, Dong-Hyun Park, Sang-Jin Lee, Young-Eun Leem, Jong-Sun Kang
Protein arginine methyltransferases (PRMTs) modulate diverse cellular processes, including stress responses. The present study explored the role of Prmt7 in protecting against menopause-associated cardiomyopathy. Mice with cardiac-specific Prmt7 ablation (cKO) exhibited sex-specific cardiomyopathy. Male cKO mice exhibited impaired cardiac function, myocardial hypertrophy, and interstitial fibrosis associated with increased oxidative stress. Interestingly, female cKO mice predominantly exhibited comparable phenotypes only after menopause or ovariectomy (OVX)...
March 14, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38480902/dysregulated-creb3-cleavage-at-the-nuclear-membrane-induces-karyoptosis-mediated-cell-death
#6
JOURNAL ARTICLE
Ga-Eun Lee, Geul Bang, Jiin Byun, Cheol-Jung Lee, Weidong Chen, Dohyun Jeung, Hyun-Jung An, Han Chang Kang, Joo Young Lee, Hye Suk Lee, Young-Soo Hong, Dae Joon Kim, Megan Keniry, Jin Young Kim, Jin-Sung Choi, Manolis Fanto, Sung-Jun Cho, Kwang-Dong Kim, Yong-Yeon Cho
Cancer cells often exhibit resistance to apoptotic cell death, but they may be vulnerable to other types of cell death. Elucidating additional mechanisms that govern cancer cell death is crucial for developing new therapies. Our research identified cyclic AMP-responsive element-binding protein 3 (CREB3) as a crucial regulator and initiator of a unique cell death mechanism known as karyoptosis. This process is characterized by nuclear shrinkage, deformation, and the loss of nuclear components following nuclear membrane rupture...
March 13, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38448692/immunopathology-of-and-potential-therapeutics-for-secondary-hemophagocytic-lymphohistiocytosis-macrophage-activation-syndrome-a-translational-perspective
#7
REVIEW
Tram T T Nguyen, Yoon Tae Kim, Geunyeol Jeong, Mirim Jin
Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a life-threatening immune disorder triggered by rheumatic disease, infections, malignancies, or medications. Characterized by the presence of hemophagocytic macrophages and a fulminant cytokine storm, sHLH/MAS leads to hyperferritinemia and multiorgan failure and rapidly progresses to death. The high mortality rate and the lack of specific treatments necessitate the development of a new drug. However, the complex and largely unknown immunopathologic mechanisms of sHLH/MAS, which involve dysfunction of various immune cells, diverse etiologies, and different clinical contexts make this effort challenging...
March 6, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38443598/the-mst1-2-bnip3-axis-is-required-for-mitophagy-induction-and-neuronal-viability-under-mitochondrial-stress
#8
JOURNAL ARTICLE
Dae Jin Jeong, Jee-Hyun Um, Young Yeon Kim, Dong Jin Shin, Sangwoo Im, Kang-Min Lee, Yun-Hee Lee, Dae-Sik Lim, Donghoon Kim, Jeanho Yun
Mitophagy induction upon mitochondrial stress is critical for maintaining mitochondrial homeostasis and cellular function. Here, we found that Mst1/2 (Stk3/4), key regulators of the Hippo pathway, are required for the induction of mitophagy under various mitochondrial stress conditions. Knockdown of Mst1/2 or pharmacological inhibition by XMU-MP-1 treatment led to impaired mitophagy induction upon CCCP and DFP treatment. Mechanistically, Mst1/2 induces mitophagy independently of the PINK1-Parkin pathway and the canonical Hippo pathway...
March 5, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38443597/extramedullary-hematopoiesis-in-cancer
#9
REVIEW
Derek A G Barisas, Kyunghee Choi
Hematopoiesis can occur outside of the bone marrow during inflammatory stress to increase the production of primarily myeloid cells at extramedullary sites; this process is known as extramedullary hematopoiesis (EMH). As observed in a broad range of hematologic and nonhematologic diseases, EMH is now recognized for its important contributions to solid tumor pathology and prognosis. To initiate EMH, hematopoietic stem cells (HSCs) are mobilized from the bone marrow into the circulation and to extramedullary sites such as the spleen and liver...
March 5, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38443596/sirt1-isgylation-accelerates-tumor-progression-by-unleashing-sirt1-from-the-inactive-state-to-promote-its-deacetylase-activity
#10
JOURNAL ARTICLE
Ji An Kang, Yoon Jung Kim, Kyu Yun Jang, Hye Won Moon, Haeseung Lee, Seonjeong Lee, Hyun Kyu Song, Sang Woo Cho, Yoon Sun Yoo, Hye Gyeong Han, Min-Ju Kim, Myoung Ja Chung, Cheol Yong Choi, Cheolju Lee, Chaeuk Chung, Gang Min Hur, You-Sun Kim, Young Joo Jeon
ISG15 is an interferon-stimulated ubiquitin-like protein (UBL) with multifaceted roles as a posttranslational modifier in ISG15 conjugation (ISGylation). However, the mechanistic consequences of ISGylation in cancer have not been fully elucidated, largely due to a lack of knowledge on the ISG15 target repertoire. Here, we identified SIRT1, a nicotinamide adenine dinucleotide (NAD+ )-dependent protein deacetylase, as a new target for ISGylation. SIRT1 ISGylation impairs the association of SIRT1 with its negative regulator, deleted in breast cancer 1 (DBC1), which unleashes SIRT1 from its inactive state and leads to an increase in its deacetylase activity...
March 5, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38443595/rebuilding-the-microenvironment-of-primary-tumors-in-humans-a-focus-on-stroma
#11
REVIEW
Siwon Mun, Hyun Jin Lee, Pilnam Kim
Conventional tumor models have critical shortcomings in that they lack the complexity of the human stroma. The heterogeneous stroma is a central compartment of the tumor microenvironment (TME) that must be addressed in cancer research and precision medicine. To fully model the human tumor stroma, the deconstruction and reconstruction of tumor tissues have been suggested as new approaches for in vitro tumor modeling. In this review, we summarize the heterogeneity of tumor-associated stromal cells and general deconstruction approaches used to isolate patient-specific stromal cells from tumor tissue; we also address the effect of the deconstruction procedure on the characteristics of primary cells...
March 5, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38443594/advances-in-single-cell-omics-and-multiomics-for-high-resolution-molecular-profiling
#12
REVIEW
Jongsu Lim, Chanho Park, Minjae Kim, Hyukhee Kim, Junil Kim, Dong-Sung Lee
Single-cell omics technologies have revolutionized molecular profiling by providing high-resolution insights into cellular heterogeneity and complexity. Traditional bulk omics approaches average signals from heterogeneous cell populations, thereby obscuring important cellular nuances. Single-cell omics studies enable the analysis of individual cells and reveal diverse cell types, dynamic cellular states, and rare cell populations. These techniques offer unprecedented resolution and sensitivity, enabling researchers to unravel the molecular landscape of individual cells...
March 5, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38433247/advances-in-cancer-dna-methylation-analysis-with-methplier-use-of-non-negative-matrix-factorization-and-knowledge-based-constraints-to-enhance-biological-interpretability
#13
JOURNAL ARTICLE
Ken Takasawa, Ken Asada, Syuzo Kaneko, Kouya Shiraishi, Hidenori Machino, Satoshi Takahashi, Norio Shinkai, Nobuji Kouno, Kazuma Kobayashi, Masaaki Komatsu, Takaaki Mizuno, Yu Okubo, Masami Mukai, Tatsuya Yoshida, Yukihiro Yoshida, Hidehito Horinouchi, Shun-Ichi Watanabe, Yuichiro Ohe, Yasushi Yatabe, Takashi Kohno, Ryuji Hamamoto
DNA methylation is an epigenetic modification that results in dynamic changes during ontogenesis and cell differentiation. DNA methylation patterns regulate gene expression and have been widely researched. While tools for DNA methylation analysis have been developed, most of them have focused on intergroup comparative analysis within a dataset; therefore, it is difficult to conduct cross-dataset studies, such as rare disease studies or cross-institutional studies. This study describes a novel method for DNA methylation analysis, namely, methPLIER, which enables interdataset comparative analyses...
March 4, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38424195/rna-m-5-c-modification-upregulates-e2f1-expression-in-a-manner-dependent-on-ybx1-phase-separation-and-promotes-tumor-progression-in-ovarian-cancer
#14
JOURNAL ARTICLE
Xiaoyi Liu, Qinglv Wei, Chenyue Yang, Hongyan Zhao, Jie Xu, Youchaou Mobet, Qingya Luo, Dan Yang, Xinzhao Zuo, Ningxuan Chen, Yu Yang, Li Li, Wei Wang, Jianhua Yu, Jing Xu, Tao Liu, Ping Yi
5-Methylcytosine (m5 C) is a common RNA modification that modulates gene expression at the posttranscriptional level, but the crosstalk between m5 C RNA modification and biomolecule condensation, as well as transcription factor-mediated transcriptional regulation, in ovarian cancer, is poorly understood. In this study, we revealed that the RNA methyltransferase NSUN2 facilitates mRNA m5 C modification and forms a positive feedback regulatory loop with the transcription factor E2F1 in ovarian cancer. Specifically, NSUN2 promotes m5 C modification of E2F1 mRNA and increases its stability, and E2F1 binds to the NSUN2 promoter, subsequently reciprocally activating NSUN2 transcription...
March 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38424194/advanced-glycation-end-products-promote-meniscal-calcification-by-activating-the-mtor-atf4-positive-feedback-loop
#15
JOURNAL ARTICLE
Sheng Yang, JiaJun Xie, ZhiJie Pan, HongMei Guan, YueSheng Tu, YuanJian Ye, ShouBin Huang, ShiQiang Fu, KangXian Li, ZhiWei Huang, XiaoQi Li, ZhanJun Shi, Le Li, Yang Zhang
The meniscus is vital for maintaining knee homeostasis and function. Meniscal calcification is one of the earliest radiological indicators of knee osteoarthritis (KOA), and meniscal calcification is associated with alterations in biomechanical properties. Meniscal calcification originates from a biochemical process similar to vascular calcification. Advanced glycation end products (AGEs) and their receptors (RAGEs) reportedly play critical roles in vascular calcification. Herein, we investigated whether targeting AGE-RAGE is a potential treatment for meniscal calcification...
March 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38424193/il-27-induced-pd-l1-high-sca-1-innate-lymphoid-cells-suppress-contact-hypersensitivity-in-an-il-10-dependent-manner
#16
JOURNAL ARTICLE
Keun Young Min, Do-Kyun Kim, Min Geun Jo, Min Yeong Choi, Dajeong Lee, Jeong Won Park, Young-Jun Park, Yeonseok Chung, Young Mi Kim, Yeong-Min Park, Hyuk Soon Kim, Wahn Soo Choi
Innate lymphoid cells (ILCs) play an important role in maintaining tissue homeostasis and various inflammatory responses. ILCs are typically classified into three subsets, as is the case for T-cells. Recent studies have reported that IL-10-producing type 2 ILCs (ILC210 s) have an immunoregulatory function dependent on IL-10. However, the surface markers of ILC210 s and the role of ILC210 s in contact hypersensitivity (CHS) are largely unknown. Our study revealed that splenic ILC210 s are extensively included in PD-L1high Sca-1+ ILCs and that IL-27 amplifies the development of PD-L1high Sca-1+ ILCs and ILC210 s...
March 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38424192/mechanical-overload-induced-release-of-extracellular-mitochondrial-particles-from-tendon-cells-leads-to-inflammation-in-tendinopathy
#17
JOURNAL ARTICLE
Ziming Chen, Mengyuan Li, Peilin Chen, Andrew Tai, Jiayue Li, Euphemie Landao Bassonga, Junjie Gao, Delin Liu, David Wood, Brendan F Kennedy, Qiujian Zheng, Ming H Zheng
Tendinopathy is one of the most common musculoskeletal diseases, and mechanical overload is considered its primary cause. However, the underlying mechanism through which mechanical overload induces tendinopathy has not been determined. In this study, we identified for the first time that tendon cells can release extracellular mitochondria (ExtraMito) particles, a subtype of medium extracellular particles (mEPs), into the environment through a process regulated by mechanical loading. RNA sequencing systematically revealed that oxygen-related reactions, extracellular particles, and inflammation were present in diseased human tendons, suggesting that these factors play a role in the pathogenesis of tendinopathy...
March 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38424191/synergistic-toxicity-with-copper-contributes-to-nat2-associated-isoniazid-toxicity
#18
JOURNAL ARTICLE
Jihoon G Yoon, Dong Geon Jang, Sung-Gyu Cho, Chaeyoung Lee, Shin Hye Noh, Soo Kyung Seo, Jung Woo Yu, Hyeon Woo Chung, KyeoRe Han, Soon Sung Kwon, Dai Hoon Han, Jaeseong Oh, In-Jin Jang, Sang-Hoon Kim, Young-Koo Jee, Hyun Lee, Dong Won Park, Jang Won Sohn, Ho Joo Yoon, Chul Hoon Kim, Jae Myun Lee, Sang-Heon Kim, Min Goo Lee
Anti-tuberculosis (AT) medications, including isoniazid (INH), can cause drug-induced liver injury (DILI), but the underlying mechanism remains unclear. In this study, we aimed to identify genetic factors that may increase the susceptibility of individuals to AT-DILI and to examine genetic interactions that may lead to isoniazid (INH)-induced hepatotoxicity. We performed a targeted sequencing analysis of 380 pharmacogenes in a discovery cohort of 112 patients (35 AT-DILI patients and 77 controls) receiving AT treatment for active tuberculosis...
March 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38424190/hypoxia-oxidative-stress-and-the-interplay-of-hifs-and-nrf2-signaling-in-cancer
#19
REVIEW
Taegeun Bae, Steffanus Pranoto Hallis, Mi-Kyoung Kwak
Oxygen is crucial for life and acts as the final electron acceptor in mitochondrial energy production. Cells adapt to varying oxygen levels through intricate response systems. Hypoxia-inducible factors (HIFs), including HIF-1α and HIF-2α, orchestrate the cellular hypoxic response, activating genes to increase the oxygen supply and reduce expenditure. Under conditions of excess oxygen and resulting oxidative stress, nuclear factor erythroid 2-related factor 2 (NRF2) activates hundreds of genes for oxidant removal and adaptive cell survival...
March 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38424189/intestinal-stem-cells-guardians-of-homeostasis-in-health-and-aging-amid-environmental-challenges
#20
REVIEW
Jiahn Choi, Leonard H Augenlicht
The intestinal epithelium is the first line of defense and acts as an interface between the vast microbial world within the gastrointestinal tract and the body's internal milieu. The intestinal epithelium not only facilitates nutrient absorption but also plays a key role in defending against pathogens and regulating the immune system. Central to maintaining a healthy epithelium are intestinal stem cells (ISCs), which are essential for replenishing the intestinal epithelium throughout an individual's lifespan...
March 1, 2024: Experimental & Molecular Medicine
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