Journal of Cellular and Molecular Medicine最新文献_第8页

RNA m5C methylation orchestrates BLCA progression via macrophage reprogramming RNA m5C甲基化通过巨噬细胞重编程协调BLCA进展

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-05 DOI: 10.1111/jcmm.17826

Dali Yan, Yongsong Xie, Liyuan Huang, Yi Zhang, Runhuan Gu, Huaibing Xie, Xing Huang, Hao Luo

{"title":"RNA m5C methylation orchestrates BLCA progression via macrophage reprogramming","authors":"Dali Yan, Yongsong Xie, Liyuan Huang, Yi Zhang, Runhuan Gu, Huaibing Xie, Xing Huang, Hao Luo","doi":"10.1111/jcmm.17826","DOIUrl":"10.1111/jcmm.17826","url":null,"abstract":"Recently, epigenetics showed essential roles in tumour microenvironment (TME) and immunotherapy response, however, the functions of RNA 5‐methylcytosine (m5C) modification in TME remains unknown. According to 13 m5C regulators, we evaluated 412 BLCA patients from The Cancer Genome Atlas (TCGA) database. The m5C score was constructed by unsupervised clustering analysis and principal component analysis (PCA) algorithms. Gene set variation analysis (GSVA), ESTIMATE algorithm, and immunohistochemical (IHC) staining were performed. Macrophage chemotaxis assay was used to assess the M2 macrophages. Among the 412 patients, the frequency of mutation was 13%. m5C regulators was expressed significantly in BLCA tissue compared with normal tissue. Then, two m5C methylation modification patterns were identified with dissimilar TME cell infiltration patterns. The C1 alteration pattern in the m5C cluster was connected with better survival. In addition, we found that NSUN6 was highly correlated with recruitment of macrophages via bioinformatics and IHC. Further experiment validated that NSUN6 promoted HDAC10 expression by mediating m5C methylation, inhibited the transcription of macrophage‐associated chemokines and thus inhibited the recruitment of M2 macrophages. The m5C score constructed by m5C modification pattern showed that high m5C score group had a better prognosis. This study uncovered the significant roles of m5C modifications in modulating the TME and indicated that NSUN6 could inhibit the recruitment of M2 macrophages via m5C methylation, which provided novel insight into epigenetic regulation of TME and clinical suggestions for immunotherapeutic strategies.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 16","pages":"2398-2411"},"PeriodicalIF":5.3,"publicationDate":"2023-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17826","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10357409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drug screening of α-amylase inhibitors as candidates for treating diabetes α-淀粉酶抑制剂治疗糖尿病的候选药物筛选

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-04 DOI: 10.1111/jcmm.17831

Meryem Alp, Alechania Misturini, German Sastre, Maria Gálvez-Llompart

{"title":"Drug screening of α-amylase inhibitors as candidates for treating diabetes","authors":"Meryem Alp, Alechania Misturini, German Sastre, Maria Gálvez-Llompart","doi":"10.1111/jcmm.17831","DOIUrl":"10.1111/jcmm.17831","url":null,"abstract":"In the present study, the identification of potential α-amylase inhibitors is explored as a potential strategy for treating type-2 diabetes mellitus. A computationally driven approach using molecular docking was employed to search for new α-amylase inhibitors. The interactions of potential drugs with the enzyme's active site were investigated and compared with the contacts established by acarbose (a reference drug for α-amylase inhibition) in the crystallographic structure 1B2Y. For this active site characterization, both molecular docking and molecular dynamics simulations were performed, and the residues involved in the α-amylase–acarbose complex were considered to analyse the potential drug's interaction with the enzyme. Two potential α-amylase inhibitors (AN-153I105594 and AN-153I104845) have been selected following this computational strategy. Both compounds established a large number of interactions with key binding site α-amylase amino acids and obtained a comparable docking score concerning the reference drug (acarbose). Aiming to further analyse candidates' properties, their ADME (absorption, distribution, metabolism, excretion) parameters, druglikeness, organ toxicity, toxicological endpoints and median lethal dose (LD50) were estimated. Overall estimations are promising for both candidates, and in silico toxicity predictions suggest that a low toxicity should be expected.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 15","pages":"2249-2260"},"PeriodicalIF":5.3,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17831","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9938177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to RDM1 promotes critical processes in breast cancer tumorigenesis 纠正RDM1促进乳腺癌肿瘤发生的关键过程

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-04 DOI: 10.1111/jcmm.17752

引用次数: 0

Correction to Down-regulation of miR-200c attenuates AngII-induced cardiac hypertrophy via targeting the MLCK-mediated pathway miR-200c下调的纠正通过靶向mlck介导的途径减轻血管内皮细胞诱导的心肌肥厚

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-03 DOI: 10.1111/jcmm.17724

引用次数: 0

A negative feedback loop between KLF9 and the EMT program dictates metastasis of hepatocellular carcinoma KLF9和EMT程序之间的负反馈回路决定了肝细胞癌的转移

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-03 DOI: 10.1111/jcmm.17823

Tao Wang, Limin Feng, Zhong Shi, Lixian Yang, Xiaofu Yu, Jinsong Wu, Jirui Sun, Jinku Zhang, Yuxiong Feng, Weilin Wang

{"title":"A negative feedback loop between KLF9 and the EMT program dictates metastasis of hepatocellular carcinoma","authors":"Tao Wang, Limin Feng, Zhong Shi, Lixian Yang, Xiaofu Yu, Jinsong Wu, Jirui Sun, Jinku Zhang, Yuxiong Feng, Weilin Wang","doi":"10.1111/jcmm.17823","DOIUrl":"10.1111/jcmm.17823","url":null,"abstract":"Metastasis is the primary cause of death of hepatocellular carcinoma (HCC), while the mechanism underlying this severe disease remains largely unclear. The Kruppel-like factor (KLF) family is one of the largest transcription factor families that control multiple physiologic and pathologic processes by governing the cellular transcriptome. To identify metastatic regulators of HCC, we conducted gene expression profiling on the MHCC97 cell series, a set of subclones of the original MHCC97 that was established by in vivo metastasis selection therefore harbouring differential metastatic capacities. We found that the expression of KLF9, a member of the KLF family, was dramatically repressed in the metastatic progeny clone of the MHCC97 cells. Functional studies revealed overexpression of KLF9 suppressed HCC migration in vitro and metastasis in vivo, while knockdown of KLF9 was sufficient to promote cell migration and metastasis accordingly. Mechanistically, we found the expression of KLF9 can reverse the pro-metastatic epithelial-mesenchymal transition (EMT) program via direct binding to the promoter regions of essential mesenchymal genes, thus repressing their expression. Interestingly, we further revealed that KLF9 was, in turn, directly suppressed by a mesenchymal transcription factor Slug, suggesting an intriguing negative feedback loop between KLF9 and the EMT program. Using clinical samples, we found that KLF9 was not only downregulated in HCC tissue compared to its normal counterparts but also further reduced in the HCC samples of whom had developed metastatic lesions. Together, we established a critical transcription factor that represses HCC metastasis, which is clinically and mechanically significant in HCC therapies.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 16","pages":"2372-2384"},"PeriodicalIF":5.3,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17823","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10026871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Pathogenic copy number variations are associated with foetal short femur length in a tertiary referral centre study 致病性拷贝数变异与胎儿股骨短长度有关在三级转诊中心的研究

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-03 DOI: 10.1111/jcmm.17821

Meiying Cai, Yanting Que, Meihuan Chen, Min Zhang, Hailong Huang, Liangpu Xu, Na Lin

{"title":"Pathogenic copy number variations are associated with foetal short femur length in a tertiary referral centre study","authors":"Meiying Cai, Yanting Que, Meihuan Chen, Min Zhang, Hailong Huang, Liangpu Xu, Na Lin","doi":"10.1111/jcmm.17821","DOIUrl":"10.1111/jcmm.17821","url":null,"abstract":"Shortened foetal femur length (FL) is a common abnormal phenotype that often causes anxiety in pregnant women, and standard clinical treatments remain unavailable. We investigated the clinical characteristics, genetic aetiology and obstetric pregnancy outcomes of foetuses with short FL and provided a reference for perinatal management of such cases. Chromosomal microarray analysis was used to analyse the copy number variations (CNV) in short FL foetuses. Of the 218 foetuses with short FL, 33 foetuses exhibited abnormal CNVs, including 19 with pathogenic CNVs and 14 with variations of uncertain clinical significance. Of the 19 foetuses with pathogenic CNVs, four had aneuploidy, 14 had deletions/duplications, and one had pathogenic uniparental diploidy. The 7q11.23 microdeletion was detected in three foetuses. The severity of short FL was not associated with the rate of pathogenic CNVs. The duration of short FL for the intrauterine ultrasound phenotype in foetuses carrying a pathogenic CNV was independent of the gestational age. Further, maternal age was not associated with the incidence of foetal pathogenic CNVs. Adverse pregnancy outcomes occurred in 77 cases, including termination of pregnancy in 63 cases, postnatal dwarfed foetuses with intellectual disability in 11 cases, and three deaths within 3 months of birth. Pathogenic CNVs closely related to foetal short FL were identified, among which the 7q11.23 microdeletion was highly associated with short FL development. This study provides a reference for the perinatal management of foetuses with short FL.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 16","pages":"2354-2361"},"PeriodicalIF":5.3,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17821","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10058847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MALAT1/miR-185-5p mediated high glucose-induced oxidative stress, mitochondrial injury and cardiomyocyte apoptosis via the RhoA/ROCK pathway MALAT1/miR-185-5p通过RhoA/ROCK途径介导高糖诱导的氧化应激、线粒体损伤和心肌细胞凋亡

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-03 DOI: 10.1111/jcmm.17835

Ting Wang, Na Li, Lingling Yuan, Mengnan Zhao, Guizhi Li, Yanxia Chen, Hong Zhou

{"title":"MALAT1/miR-185-5p mediated high glucose-induced oxidative stress, mitochondrial injury and cardiomyocyte apoptosis via the RhoA/ROCK pathway","authors":"Ting Wang, Na Li, Lingling Yuan, Mengnan Zhao, Guizhi Li, Yanxia Chen, Hong Zhou","doi":"10.1111/jcmm.17835","DOIUrl":"10.1111/jcmm.17835","url":null,"abstract":"To explore the underlying mechanism of lncRNA MALAT1 in the pathogenesis of diabetic cardiomyopathy (DCM). DCM models were confirmed in db/db mice. MiRNAs in myocardium were detected by miRNA sequencing. The interactions of miR-185-5p with MALAT1 and RhoA were validated by dual-luciferase reporter assays. Primary neonatal cardiomyocytes were cultured with 5.5 or 30 mmol/L D-glucose (HG) in the presence or absence of MALAT1-shRNA and fasudil, a ROCK inhibitor. MALAT1 and miR-185-5p expression were determined by real-time quantitative PCR. The apoptotic cardiomyocytes were evaluated using flow cytometry and TUNEL staining. SOD activity and MDA contents were measured. The ROCK activity, phosphorylation of Drp1S616, mitofusin 2 and apoptosis-related proteins were analysed by Western blotting. Mitochondrial membrane potential was examined by JC-1. MALAT1 was significantly up-regulated while miR-185-5p was down-regulated in myocardium of db/db mice and HG-induced cardiomyocytes. MALAT1 regulated RhoA/ROCK pathway via sponging miR-185-5p in cardiomyocytes in HG. Knockdown of MALAT1 and fasudil all inhibited HG-induced oxidative stress, and alleviated imbalance of mitochondrial dynamics and mitochondrial dysfunction, accompanied by reduced cardiomyocyte apoptosis. MALAT1 activated the RhoA/ROCK pathway via sponging miR-185-5p and mediated HG-induced oxidative stress, mitochondrial damage and apoptosis of cardiomyocytes in mice.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 17","pages":"2495-2506"},"PeriodicalIF":5.3,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17835","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10177948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

LncRNA-HOTAIR promotes endothelial cell pyroptosis by regulating the miR-22/NLRP3 axis in hyperuricemia LncRNA-HOTAIR通过调节miR-22/NLRP3轴在高尿酸血症中促进内皮细胞热亡

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-02 DOI: 10.1111/jcmm.17777

引用次数: 0

GP-2250, a novel anticancer agent, inhibits the energy metabolism, activates AMP-Kinase and impairs the NF-kB pathway in pancreatic cancer cells GP-2250是一种新型抗癌药物，可抑制胰腺癌细胞的能量代谢，激活amp激酶并损害NF-kB通路

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-06-30 DOI: 10.1111/jcmm.17825

Britta Majchrzak-Stiller, Marie Buchholz, Ilka Peters, Daniel Waschestjuk, Johanna Strotmann, Philipp Höhn, Stephan Hahn, Chris Braumann, Waldemar Uhl, Thomas Müller, Hanns Möhler

{"title":"GP-2250, a novel anticancer agent, inhibits the energy metabolism, activates AMP-Kinase and impairs the NF-kB pathway in pancreatic cancer cells","authors":"Britta Majchrzak-Stiller, Marie Buchholz, Ilka Peters, Daniel Waschestjuk, Johanna Strotmann, Philipp Höhn, Stephan Hahn, Chris Braumann, Waldemar Uhl, Thomas Müller, Hanns Möhler","doi":"10.1111/jcmm.17825","DOIUrl":"10.1111/jcmm.17825","url":null,"abstract":"GP-2250, a novel anticancer agent, severely limits the energy metabolism, as demonstrated by the inhibition of hexokinase 2 and glyceraldehyde-3-phosphate dehydrogenase and a decrease of ATP. Rescue experiments with supplementary pyruvate or oxaloacetate demonstrated that a TCA cycle deficit largely contributed to cytotoxicity. Activation of the energy-deficit sensor, AMP-dependent protein kinase, was associated with increased phosphorylation of acetyl-CoA carboxylase and Raptor, pointing to a possible deficit in the synthesis of fatty acids and proteins as essential cell components. Binding of p65 to DNA was dose-dependently reduced in nuclear lysates. A transcriptional deficit of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) was substantiated by the downregulation of cyclin D1 and of the anti-apoptotic Bcl2, in line with reduction in tumour cell proliferation and induction of apoptosis, respectively. The upregulation of p53 concomitant with an excess of ROS supported apoptosis. Thus, the anticancer activity of GP-2250 is a result of disruption of energy metabolism and inhibition of tumour promotion by NF-κB.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 14","pages":"2082-2092"},"PeriodicalIF":5.3,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17825","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9803609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Contribution of PGAP3 co-amplified and co-overexpressed with ERBB2 at 17q12 involved poor prognosis in gastric cancer PGAP3与ERBB2在17q12位点的共扩增和共过表达参与了胃癌的不良预后

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-06-29 DOI: 10.1111/jcmm.17828

Dong Wang, Siyu Hao, Hongjie He, Jian Zhang, Ge You, Xin Wu, Rui Zhang, Xiangning Meng, Xiaobo Cui, Jing Bai, Songbin Fu, Jingcui Yu

{"title":"Contribution of PGAP3 co-amplified and co-overexpressed with ERBB2 at 17q12 involved poor prognosis in gastric cancer","authors":"Dong Wang, Siyu Hao, Hongjie He, Jian Zhang, Ge You, Xin Wu, Rui Zhang, Xiangning Meng, Xiaobo Cui, Jing Bai, Songbin Fu, Jingcui Yu","doi":"10.1111/jcmm.17828","DOIUrl":"10.1111/jcmm.17828","url":null,"abstract":"The locus at 17q12 erb-b2 receptor tyrosine kinase 2 (ERBB2) has been heavily amplificated and overexpressed in gastric cancer (GC), but it remains to be elucidated about the clinical significance of the co-amplification and co-overexpression of PGAP3 gene located around ERBB2 in GC. The profile of PGAP3 and ERBB2 in four GC cell lines and tissue microarrays containing 418 primary GC tissues was assessed to investigate the co-overexpression and clinical significance of the co-amplified genes, and to evaluate the impact of the co-amplified genes on the malignancy of GC. Co-amplification of PGAP3 and ERBB2 accompanied with co-overexpression was observed in a haploid chromosome 17 of NCI-N87 cells with double minutes (DMs). PGAP3 and ERBB2 were overexpressed and positively correlated in 418 GC patients. Co-overexpression of the PGAP3 and ERBB2 was correlated with T stage, TNM stage, tumour size, intestinal histological type and poor survival proportion in 141 GC patients. In vitro, knockdown of the endogenous PGAP3 or ERBB2 decreased cell proliferation and invasion, increased G1 phase accumulation and induced apoptosis in NCI-N87 cells. Furthermore, combined silencing of PGAP3 and ERBB2 showed an additive effect on resisting proliferation of NCI-N87 cells compared with targeting ERBB2 or PGAP3 alone. Taken together, the co-overexpression of PGAP3 and ERBB2 may be crucial due to its significant correlation with clinicopathological factors of GC. Haploid gain of PGAP3 co-amplified with ERBB2 is sufficient to facilitate the malignancy and progression of GC cells in a synergistic way.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 16","pages":"2424-2436"},"PeriodicalIF":5.3,"publicationDate":"2023-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17828","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10001472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1