Experimental cell research最新文献_第5页

METTL14-mediated m6A methylation regulates pathological retinal neovascularization by targeting autophagy METTL14 介导的 m6A 甲基化通过靶向自噬调节病理性视网膜新生血管。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-10-24 DOI: 10.1016/j.yexcr.2024.114291

Yang Yu , Huiling Nie , Xun Qin , Xi Chen , Xiumiao Li , Jin Yao

{"title":"METTL14-mediated m6A methylation regulates pathological retinal neovascularization by targeting autophagy","authors":"Yang Yu , Huiling Nie , Xun Qin , Xi Chen , Xiumiao Li , Jin Yao","doi":"10.1016/j.yexcr.2024.114291","DOIUrl":"10.1016/j.yexcr.2024.114291","url":null,"abstract":"<div><div>Pathological retinal neovascularization (RNV) is a prevalent characteristic of various ocular diseases, including proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and retinal vein occlusion (RVO). While the importance of N6-methyladenosine (m6A) modification in diverse disease contexts is well-established, its functional role in pathological RNV remains unclear. Herein, we investigated the involvement of m6A modification and its core methyltransferase, METTL14, in a model of oxygen-induced retinopathy (OIR) to elucidate their contribution to retinal angiogenesis. In this study, we observed heightened levels of m6A modification and elevated expression of METTL14 in the OIR model, suggesting their potential implication in pathological RNV. Employing targeted knockdown of METTL14, we revealed that its depletion activated autophagy flux in human retinal vascular endothelial cells (HRVECs), consequently inhibiting the angiogenic capacity of endothelial cells. Mechanistically, we demonstrated that METTL14 exerts its regulatory influence on autophagy flux by modulating the stability of ATG7, a pivotal protein involved in autophagy. Specifically, METTL14 knockdown led to increased ATG7 expression at both mRNA and protein levels, accompanied by reduced m6A methylation of ATG7 mRNA and enhanced mRNA stability. Moreover, silencing of ATG7 counteracted the effects of METTL14 knockdown on endothelial cell functions, emphasizing ATG7 as a downstream target of METTL14-mediated autophagy in HRVECs. After all, our findings provide valuable insights into the pathogenesis of retinal pathological angiogenesis and potential therapeutic targets for the treatment of ocular neovascular diseases.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"443 1","pages":"Article 114291"},"PeriodicalIF":3.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Downregulation of heat shock protein 47 caused lysosomal dysfunction leading to excessive chondrocyte apoptosis 热休克蛋白 47 的下调会导致溶酶体功能障碍，从而导致软骨细胞过度凋亡。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-10-22 DOI: 10.1016/j.yexcr.2024.114294

Yawen Shi , Ying He , Yanan Li , Meng Zhang , Yinan Liu , Hui Wang , Zhiran Shen , Xiaoru Zhao , Rui Wang , Tianyou Ma , Pinglin Yang , Jinghong Chen

{"title":"Downregulation of heat shock protein 47 caused lysosomal dysfunction leading to excessive chondrocyte apoptosis","authors":"Yawen Shi , Ying He , Yanan Li , Meng Zhang , Yinan Liu , Hui Wang , Zhiran Shen , Xiaoru Zhao , Rui Wang , Tianyou Ma , Pinglin Yang , Jinghong Chen","doi":"10.1016/j.yexcr.2024.114294","DOIUrl":"10.1016/j.yexcr.2024.114294","url":null,"abstract":"<div><div>Heat shock protein 47 (HSP47) is a collagen-specific chaperone present in several regions of the endoplasmic reticulum and cytoplasm. Elevated HSP47 expression in cells causes various cancers and fibrotic disorders. However, the consequences of HSP47 downregulation leading to chondrocyte death, as well as the underlying pathways, remain largely unclear. This study presents the first experimental evidence of the localization of HSP47 on lysosomes. Additionally, it successfully designed and generated shRNA HSP47 target sequences to suppress the expression of HSP47 in ATDC5 chondrocytes using lentiviral vectors. By employing a chondrocyte model that has undergone stable downregulation of HSP47, we observed that HSP47 downregulation in chondrocytes, disturbs the acidic homeostatic environment of chondrocyte lysosomes, causes hydrolytic enzyme activity dysregulation, impairs the lysosome-mediated autophagy-lysosome pathway, and causes abnormal expression of lysosomal morphology, number, and functional effector proteins. This implies the significance of the presence of HSP47 in maintaining proper lysosomal function. Significantly, the inhibitor CA-074 Me, which can restore the dysfunction of lysosomes, successfully reversed the negative effects of HSP47 on the autophagy-lysosomal pathway and partially reduced the occurrence of excessive cell death in chondrocytes. This suggests that maintaining proper lysosomal function is crucial for preventing HSP47-induced apoptosis in chondrocytes. The existence of HSP47 is crucial for preserving optimal lysosomal function and autophagic flux, while also inhibiting excessive apoptosis in ATDC5 chondrocytes.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"443 1","pages":"Article 114294"},"PeriodicalIF":3.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ALKBH5 promotes T-cell acute lymphoblastic leukemia growth via m⁶A-guided epigenetic inhibition of miR-20a-5p. ALKBH5 通过 m6A 引导的 miR-20a-5p 表观遗传抑制作用促进 T 细胞急性淋巴细胞白血病的生长。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-10-21 DOI: 10.1016/j.yexcr.2024.114293

Jiazhuo Liu, Xin Zhang, Yi Liao, Chunlan Zhang, Leiwen Peng

{"title":"ALKBH5 promotes T-cell acute lymphoblastic leukemia growth via m<sup>6</sup>A-guided epigenetic inhibition of miR-20a-5p.","authors":"Jiazhuo Liu, Xin Zhang, Yi Liao, Chunlan Zhang, Leiwen Peng","doi":"10.1016/j.yexcr.2024.114293","DOIUrl":"https://doi.org/10.1016/j.yexcr.2024.114293","url":null,"abstract":"<p><p>This study investigates the role of ALKBH5-mediated m<sup>6</sup>A demethylation in T-cell acute lymphoblastic leukemia (T-ALL). T-ALL cell lines (HPB-ALL, MOLT4, Jurkat, CCRF-CEM) and human T cells were analyzed. CCRF-CEM and Jurkat cells were transfected with si-ALKBH5, miR-20a-5p-inhibitor, and pcDNA3.1-DDX5. The expression levels of ALKBH5, miR-20a-5p, and DDX5 in these cells were determined using qRT-PCR and Western blotting. Cell viability, proliferation, colony formation, and apoptosis were assessed using CCK-8, EdU staining, colony formation assay, and flow cytometry. mRNA m6A levels were quantified with an m6A RNA methylation detection reagent, and RNA immunoprecipitation was employed to measure the enrichment of DGCR8 and m6A on the primary transcript pri-miR-20a of miR-20a-5p. Dual-luciferase assay confirmed the binding relationship between miR-20a-5p and DDX5. Results showed that ALKBH5 and DDX5 were upregulated in T-ALL tissues and cells, whereas miR-20a-5p was downregulated. Silencing ALKBH5 inhibited T-ALL cell viability, colony formation, and proliferation, while promoting apoptosis. These effects were reversed by miR-20a-5p inhibition or DDX5 overexpression. ALKBH5 reduced the relative m<sup>6</sup>A level in T-ALL cells and decreased miR-20a-5p expression by reducing DGCR8 binding to pri-miR-20a-5p. miR-20a-5p suppressed DDX5 transcription. In conclusion, ALKBH5-mediated m<sup>6</sup>A demethylation decreases DGCR8 binding to pri-miR-20a, thereby repressing miR-20a-5p expression and enhancing DDX5 expression, ultimately inhibiting T-ALL cell apoptosis and promoting proliferation.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"114293"},"PeriodicalIF":3.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TIPE2 aggravates experimental colitis and disrupts intestinal epithelial barrier integrity by activating JAK2/STAT3/SOCS3 signal pathway TIPE2 通过激活 JAK2/STAT3/SOCS3 信号通路，加重实验性结肠炎并破坏肠上皮屏障的完整性。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-10-18 DOI: 10.1016/j.yexcr.2024.114287

Lingli Zeng , Yuping Wang , Jiaxin Shen , Xujin Wei , Yilong Wu , Xintong Chi , Xueyan Zheng , Xing Yu , Ying Shi , Wenming Liu

{"title":"TIPE2 aggravates experimental colitis and disrupts intestinal epithelial barrier integrity by activating JAK2/STAT3/SOCS3 signal pathway","authors":"Lingli Zeng , Yuping Wang , Jiaxin Shen , Xujin Wei , Yilong Wu , Xintong Chi , Xueyan Zheng , Xing Yu , Ying Shi , Wenming Liu","doi":"10.1016/j.yexcr.2024.114287","DOIUrl":"10.1016/j.yexcr.2024.114287","url":null,"abstract":"<div><div>Ulcerative colitis (UC) is a chronic relapsing and progressive inflammatory disease of the colon. TIPE2 is a negative regulator of innate and adaptive immunity that maintains immune homeostasis. We found that TIPE2 was highly expressed in mucosa of mice with colitis. However, the role of TIPE2 in colitis remains unclear. We induced colitis in mice with dextran sulfate sodium (DSS) and treated them with TIPE2, and investigated the inflammatory activity of the colon <em>in vivo</em> by cytokines detection and histopathological analyses. We also measured inflammatory alteration and tight junctions induced by DSS <em>in vitro</em>. The results demonstrated that administration of TIPE2 promoted the severity of colitis in mice and human colon epithelial cells. Furthermore, TIPE2 aggravated intestinal epithelial barrier dysfunction by decreasing the expression of the tight junction proteins Occludin, Claudin-1 and ZO-1. In addition, TIPE2 exacerbated intestinal inflammatory response by inhibiting the expression of SOCS3, remarkably activating JAK2/STAT3 signaling pathway, and increasing the translocation of phosphorylated STAT3 into the nucleus. Silencing of <em>TIPE2</em> attenuated the DSS-induced activation of JAK2/STAT3, thereby rescuing epithelial inflammatory injury and restoring barrier dysfunction. These results indicate that TIPE2 augments experimental colitis and disrupted the integrity of the intestinal epithelial barrier by activating the JAK2/STAT3/SOCS3 signaling pathway.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"443 1","pages":"Article 114287"},"PeriodicalIF":3.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cellular resiliency and survival of Neuro-2a cells under extreme stress 神经-2a 细胞系在极端压力下的细胞恢复能力和存活率

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-10-09 DOI: 10.1016/j.yexcr.2024.114275

Randall Hernandez-Jimenez , Ankit Patel , Ana Machado-Olavarria , Hailey Mathieu , Jessica Wohlfahrt , Jennifer Guergues , Stanley M. Stevens , Ashutosh Dharap

{"title":"Cellular resiliency and survival of Neuro-2a cells under extreme stress","authors":"Randall Hernandez-Jimenez , Ankit Patel , Ana Machado-Olavarria , Hailey Mathieu , Jessica Wohlfahrt , Jennifer Guergues , Stanley M. Stevens , Ashutosh Dharap","doi":"10.1016/j.yexcr.2024.114275","DOIUrl":"10.1016/j.yexcr.2024.114275","url":null,"abstract":"<div><div>Stressors such as hypoxia, hypothermia, and acute toxicity often result in widespread cell death. This study investigated the outcomes of Neuro-2a (N2a; mouse neuroblastoma) cells following a cryogenic storage failure that exposed them to a combination of these stressors over a period of approximately 24-30 hours. Remarkably, a small fraction of the cells survived the event, underwent a period of dormancy, and eventually recovered to a healthy state. To understand the underlying resilience mechanisms, we created a model to replicate the dewar failure event and examined changes in phenotype, transcriptomics, proteomics, and mitochondrial activity of the surviving cells during recovery. We found that the surviving cells initially displayed a stressed morphology with irregular membranes and a clustered apperance. They showed an increased expression of proteins related to DNA repair and chromatin modification pathways as well as heightened mitochondrial function shortly after the stress event. As recovery progressed, the stress-responsive pathways, mitochondrial activity, and growth rates normalized toward that of healthy controls, indicating a return to a stable baseline state. These findings suggest that an initial robust energetic state supports key stress-responsive and repair pathways at the early stages of recovery, facilitating cell survival and resiliency after extreme stress. This work provides valuable insights into cellular resilience mechanisms with potential implications for improving cell preservation and recovery in biomedical applications and developing therapeutic strategies for conditions involving cell damage and stress.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"443 1","pages":"Article 114275"},"PeriodicalIF":3.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deficiency in the Rab25 gene leads to a decline in male fertility and testicular injury: Impact on the regulation of germ cell proliferation and apoptosis Rab25 基因缺陷会导致男性生育能力下降和睾丸损伤：对生殖细胞增殖和凋亡调控的影响

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-10-01 DOI: 10.1016/j.yexcr.2024.114285

Qiang Zhang , Zhicheng Zhang , Zhenmin Liu , Chong Wang , Hongsong Chen , Lianju Shen , Chunlan long , Guanghui Wei , Xing Liu

{"title":"Deficiency in the Rab25 gene leads to a decline in male fertility and testicular injury: Impact on the regulation of germ cell proliferation and apoptosis","authors":"Qiang Zhang , Zhicheng Zhang , Zhenmin Liu , Chong Wang , Hongsong Chen , Lianju Shen , Chunlan long , Guanghui Wei , Xing Liu","doi":"10.1016/j.yexcr.2024.114285","DOIUrl":"10.1016/j.yexcr.2024.114285","url":null,"abstract":"<div><h3>Background</h3><div>Rab25 is a member of the Rab family, functioning as a regulatory molecule in intracellular transport. Although its involvement in cellular functions and disease development is well-established, its precise roles in male reproductive physiology remain elusive.</div></div><div><h3>Methods</h3><div>To explore the specific roles of Rab25 in testicular development and spermatogenesis, we established the Rab25<sup>−/−</sup> mouse model and Rab25 knockdown germ cell line (GC-2). We compared the fertility, sperm analysis, and testicular tissues between Rab25<sup>−/−</sup> and wild-type male mice. To delve deeper into potential mechanisms, we employed immunohistochemistry, TUNEL assay, Western Blotting, CCK-8 assay, etc. to evaluate cell proliferation and apoptosis in testicular tissues and GC-2 cells.</div></div><div><h3>Results</h3><div>Our findings indicated that Rab25 was expressed in germ cells and Leydig cells in the testes. Although the weight of Rab25<sup>−/−</sup> mice testes exhibited no significant changes, fertility was compromised, with a decrease in sperm quantity and reduced motility. HE staining revealed a disorganized arrangement of germ cells and vacuolization. Additionally, chromatin marginalization and nuclear pyknosis were observed in the Rab25<sup>−/−</sup> mice. In both Rab25<sup>−/−</sup> mice testes and Rab25 knockdown GC-2 cells, we found that germ cell proliferation was reduced, while apoptosis was increased.</div></div><div><h3>Conclusions</h3><div>In conclusion, our study proposes that Rab25 plays a vital role in spermatogenesis by regulating the proliferation and apoptosis of germ cells.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114285"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exercise training alleviates cholesterol and lipid accumulation in mice with non-alcoholic steatohepatitis: Reduction of KMT2D-mediated histone methylation of IDI1 运动训练可减轻非酒精性脂肪性肝炎小鼠的胆固醇和脂质积累：减少 KMT2D 介导的 IDI1 组蛋白甲基化。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-10-01 DOI: 10.1016/j.yexcr.2024.114265

Xiuqin Fan , Hongshi Wang , Weiwei Wang , Jiayan Shen , Zejun Wang

{"title":"Exercise training alleviates cholesterol and lipid accumulation in mice with non-alcoholic steatohepatitis: Reduction of KMT2D-mediated histone methylation of IDI1","authors":"Xiuqin Fan , Hongshi Wang , Weiwei Wang , Jiayan Shen , Zejun Wang","doi":"10.1016/j.yexcr.2024.114265","DOIUrl":"10.1016/j.yexcr.2024.114265","url":null,"abstract":"<div><div>Exercise training is a cornerstone treatment for non-alcoholic fatty liver disease (NAFLD). This study aims to investigate the effects of exercises on lipid accumulation in non-alcoholic steatohepatitis (NASH) and to explore the molecular mechanism. Established NASH mice were remained sedentary or subjected to moderate-intensity continuous training or high-intensity interval training (HIIT). The two training regimens, especially the latter one, reduced liver weight, steatosis, inflammation, lipid accumulation, collagen deposition, and cholesterol content in the mouse liver. Similarly, the HIIT regimen improved clinical presentation of NAFLD patients. RNA sequencing analysis revealed lysine methyltransferase 2D (Kmt2d) and isopentenyl-diphosphate delta isomerase 1 (Idi1) as two important genes downregulated in mice underwent HIIT. By using mouse hepatocytes AML12, we found that KMT2D promoted <em>Idi1</em> expression by catalyzing H3K4me1 modification near its promoter. Upregulation of either KMT2D or IDI1 blocked the ameliorating effects of HIIT on mice. Meanwhile, in AML12 cells modeled by palmitic acid and oleic acid treatment, KMT2D and IDI1 were found to be correlated with lipid accumulation, cholesterol content, inflammation, and cell death and senescence. In conclusion, this study demonstrates that the ameliorating effects of exercise training on NASH might involve the downregulation of the KMT2D/IDI1 axis.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114265"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The emerging role of miRNAs in pituitary adenomas: From molecular signatures to diagnostic potential miRNA 在垂体腺瘤中的新作用：从分子特征到诊断潜力。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-10-01 DOI: 10.1016/j.yexcr.2024.114279

Ahmed S. Doghish , Gharieb S. El-Sayyad , Sherif S. Abdel Mageed , Mai A. Abd-Elmawla , Al-Aliaa M. Sallam , Manar Mohammed El Tabaa , Nehal I. Rizk , Alaa Ashraf , Osama A. Mohammed , Safwat Abdelhady Mangoura , Tohada M. AL-Noshokaty , Mohamed Bakr Zaki , Walaa A. El-Dakroury , Mahmoud A. Elrebehy , Mustafa Ahmed Abdel-Reheim , Mohammed S. Elballal , Ahmed I. Abulsoud

{"title":"The emerging role of miRNAs in pituitary adenomas: From molecular signatures to diagnostic potential","authors":"Ahmed S. Doghish , Gharieb S. El-Sayyad , Sherif S. Abdel Mageed , Mai A. Abd-Elmawla , Al-Aliaa M. Sallam , Manar Mohammed El Tabaa , Nehal I. Rizk , Alaa Ashraf , Osama A. Mohammed , Safwat Abdelhady Mangoura , Tohada M. AL-Noshokaty , Mohamed Bakr Zaki , Walaa A. El-Dakroury , Mahmoud A. Elrebehy , Mustafa Ahmed Abdel-Reheim , Mohammed S. Elballal , Ahmed I. Abulsoud","doi":"10.1016/j.yexcr.2024.114279","DOIUrl":"10.1016/j.yexcr.2024.114279","url":null,"abstract":"<div><div>Pituitary adenomas (PAs) are an array of tumors originating from the pituitary gland. PAs are sorted as functional or nonfunctional according to their hormonal activity and classified according to size into microadenomas and macroadenomas. Still, the cellular events that trigger the transformations in pituitary neoplasms are not fully understood, and the current classification methods do not precisely predict clinical behavior. A rising number of researches have emphasized the role of miRNAs, that drawn more attention as oncogenic molecules or tumor suppressors. The etiopathological mechanisms of PAs include multiple molecular cascades that are influenced by different miRNAs. miRNAs control the cell cycle control, pro- or antiapoptotic processes, and tumor invasion and metastasis. miRNAs offer a novel perspective on tumor features and behaviors and might be valuable in prognostication and therapeutic plans. In pituitary adenomas, miRNAs showed a specific expression pattern depending on their size, cell origin, remission, and treatments. Screening miRNA expression patterns is promising to monitor and evaluate recurrence, as well as to investigate the efficacy of radiation and chemotherapy for PAs exhibiting aggressive behavior. Thus, the current review investigated the interplay of the miRNAs' pivotal role in offering new opportunities to translate these innovative epigenetic tools into healthcare applications.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114279"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exosomal microRNA-363 mediates the destructive effect of M1 macrophages on chondrocytes by repressing G3BP2 外泌体 microRNA-363 通过抑制 G3BP2 来介导 M1 巨噬细胞对软骨细胞的破坏作用。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-10-01 DOI: 10.1016/j.yexcr.2024.114276

Wenteng Si , Hongchao Wei , Wenzhong Chen , Bin Chen , Yu Zhou , Huaguo Zhang

{"title":"Exosomal microRNA-363 mediates the destructive effect of M1 macrophages on chondrocytes by repressing G3BP2","authors":"Wenteng Si , Hongchao Wei , Wenzhong Chen , Bin Chen , Yu Zhou , Huaguo Zhang","doi":"10.1016/j.yexcr.2024.114276","DOIUrl":"10.1016/j.yexcr.2024.114276","url":null,"abstract":"<div><div>M1 polarization of synovial macrophages contributes to cartilage degeneration and osteoarthritis (OA) development. However, limited knowledge is available about how M1 macrophages affect the biological properties of chondrocytes. This study aimed to explore the role of exosomal microRNAs (miRs) released from M1 macrophages in modulating the proliferation and survival of chondrocytes. Through bioinformatic analysis and experimental validation, we indicated that miR-363 was selectively induced in M1 macrophages (CD68<sup>+</sup>CD80<sup>+</sup>) but not M2 macrophages (CD68<sup>+</sup>CD206<sup>+</sup>). The upregulation of miR-363 in M1 macrophages depended on the activation of STAT1 signaling. Clinically, OA patients had a significantly higher miR-363 level in synovial fluid than control individuals without OA. Functional studies revealed that inhibition of miR-363 blocked the M1 macrophage polarization induced by lipopolysaccharide and IFN-γ. Moreover, exosomal miR-363 released from M1 macrophages significantly suppressed the proliferation and survival and induced inflammatory gene expression in chondrocytes. G3BP2 was identified as a target gene for miR-363 and could be negatively regulated by miR-363. Knockdown of G3BP2 recapitulated the effect of miR-363 overexpression on chondrocytes. Most importantly, enforced expression of G3BP2 attenuated miR-363-induced apoptosis and inflammatory response in chondrocytes. In conclusion, miR-363 plays an indispensable role in M1 macrophage polarization and can be released from M1 macrophages via exosomes to cause chondrocyte injury and inflammation. The miR-363/G3BP2 axis may represent a promising target for the prevention of OA development.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114276"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Particular exosomal micro-RNAs and gastrointestinal (GI) cancer cells' roles: Current theories 特殊外泌体微RNA与胃肠道（GI）癌细胞的作用：目前的理论。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-10-01 DOI: 10.1016/j.yexcr.2024.114278

Bandar Almutairy , Mohammad S. Alzahrani , Dania S. Waggas , Hashem O. Alsaab

{"title":"Particular exosomal micro-RNAs and gastrointestinal (GI) cancer cells' roles: Current theories","authors":"Bandar Almutairy , Mohammad S. Alzahrani , Dania S. Waggas , Hashem O. Alsaab","doi":"10.1016/j.yexcr.2024.114278","DOIUrl":"10.1016/j.yexcr.2024.114278","url":null,"abstract":"<div><div>A diverse range of gastrointestinal tract disorders are called gastrointestinal (GI) malignancies. The transformation of normal cells into precursor cells, precursor cells into premalignant cells, and premalignant cells into cancerous cells is facilitated by the interaction of many modifiable and non-modifiable risk factors. Developing relevant therapy alternatives based on a better knowledge of the illness's aetiology is essential to enhance patient outcomes. The exosome is crucial in regulating intercellular interaction because it may send molecular signals to nearby or distant cells. Exosomes produced from cancer can introduce a variety of chemicals and vast concentrations of microRNA (miRNA) into the tumour microenvironment. These miRNAs significantly impact immunological evasion, metastasis, apoptosis resistance, and cell growth. Exosomal miRNAs, or exosomal miRNAs, are essential for controlling cancer resistance to apoptosis, according to mounting data. Exosomal miRNAs function as an interaction hub between cancerous cells and the milieu around them, regulating gene expression and various signalling pathways. Our research examines the regulatory function of exosomal miRNAs in mediating interactions between cancer cells and the stromal and immunological cells that make up the surrounding milieu.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114278"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0