Journal of Molecular Histology最新文献

{"title":"hsa_circ_0001103 correlates with unfavorable MRI features and promotes glioma progression by modulating the miR-375/YAP1 axis","authors":"Yu Hong,&nbsp;Lijun Liu,&nbsp;Yuedong Hai,&nbsp;Liwei Bao","doi":"10.1007/s10735-025-10445-z","DOIUrl":"10.1007/s10735-025-10445-z","url":null,"abstract":"<div><p>To investigate the role of circ_0001103 in glioma and its underlying molecular mechanism. Differentially expressed circRNAs in glioblastoma cells and neural progenitor cells were analyzed with the data of GSE146463. Tissues samples, clinicopathological parameters and MRI characteristics were retrospectively collected. Circ_0001103, miR-375 and YAP1 expression levels were measured by qRT-PCR and Western blot. The relationship between circ_0001103 expression and clinicopathological parameters or MRI features of glioma patients was analyzed by chi-square test. After circ_0001103 or miR-375 was selectively up-regulated or down-regulated, CCK-8 assay, BrdU assay and flow cytometry were used to detect the proliferation and apoptosis of glioma cells. Bioinformatics prediction, dual-luciferase reporter gene assay and RNA immunoprecipitation were executed to verify the targeting relationships among miR-375, circ_0001103 and YAP1 3’ UTR. circ_0001103 was significantly up-regulated in glioma tissues and cell lines, which was positively correlated with the larger tumor size and non-uniform signal in MRI. Overexpression of circ_0001103 promoted glioma cell proliferation and inhibited apoptosis, while knockdown of circ_0001103 worked oppositely. Circ_0001103 negatively regulated miR-375 expression. MiR-375 targeted YAP1, and YAP1 was indirectly and positively modulated by circ_0001103. Circ_0001103 expression was negatively correlated with miR-375 expressions, while positively correlated with YAP1 expression in glioma tissues. Circ_0001103 contributes to glioma progression by regulating miR-375/YAP1 axis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-29a-3p compositely regulates the COL6A6/PTEN-PI3K/Akt/CUX1 feedback loop to participate in the proliferation and invasion of pituitary adenomas","authors":"Zhuohui Liu,&nbsp;Xiufu Liao,&nbsp;Hexiang Zhao,&nbsp;Biao Ruan,&nbsp;Fengfeng Jia,&nbsp;Xuzhi He,&nbsp;Ruiqing Long","doi":"10.1007/s10735-025-10436-0","DOIUrl":"10.1007/s10735-025-10436-0","url":null,"abstract":"<div><p>Pituitary adenoma (PA) is one of the most common intracranial tumors, and owing to its special biological morphology and behavior, there is currently no effective treatment. miRNAs play crucial roles as diagnostic indicators and targets for the treatment of numerous cancer types. The objective of this research was to explore how miR-29a-3p influences the development of PA. We collected 25 pairs of PA tissue and normal pituitary tissue, followed by the subcutaneous injection of 5 × 10⁷ HP75 cells into the left axilla of nude mice, creating a heterotopic PA xenograft tumor model for experimental study. TtT/GF and HP75 cell proliferation and tumor growth in nude mice were assessed using CCK-8, Transwell, and immunohistochemistry tests. Western blotting, RT‒qPCR and RIP were used to detect the expression and interaction of related proteins and genes. The expression of miR-29a-3p was upregulated in PA. Knockdown of miR-29a-3p can inhibit the proliferation, invasion and migration of TtT/GF and HP75 cells and reduce the epithelial mesenchymal transformation (EMT) of these cells. Furthermore, reducing miR-29a-3p levels suppressed the expression of Ki-67 in the PA tissues of nude mice and slowed tumor growth. From a mechanistic standpoint, miR-29a-3p can target COL6A6 and PTEN. Knockdown of miR-29a-3p inhibits the PI3K/Akt/CUX1 signaling pathway through simultaneously increasing COL6A6 and PTEN expression, thus inhibiting the proliferation, invasion, migration and EMT of PA cells and alleviating the progression of PA. Conversely, CUX1 can promote the expression of miR-29a-3p through a positive feedback loop and accelerate the development of PA. Our study suggests that downregulating the expression of miR-29a-3p may be a new target for the treatment of PA.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-025-10436-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long non-coding RNA HOXA11-AS inhibits apoptosis, induces proliferation, and promotes autophagy via the miR-214-3p/ATG12 axis in acute T lymphoblastic leukemia","authors":"Rui Zhang,&nbsp;YuanYuan Zhang,&nbsp;XiaoFei Li,&nbsp;ShaoHua Wang,&nbsp;Jiao Li,&nbsp;ShuoChun Shao,&nbsp;Bin Liu,&nbsp;WeiWei Guo,&nbsp;Min Shi","doi":"10.1007/s10735-025-10462-y","DOIUrl":"10.1007/s10735-025-10462-y","url":null,"abstract":"<div><p>Acute T lymphocytic leukemia (T-ALL) is a hematological cancer with high mortality. The literature suggests an association between T-ALL and Long non-coding RNAs (lncRNAs). Nevertheless, the mechanism of lncRNA HOXA11-AS in T-ALL remains undetermined. The lncRNA HOXA11-AS expression level were assessed in T-ALL patients and normal controls by qRT-PCR. Furthermore, The proliferation, apoptosis, and autophagy of T-ALL cell (Molt4 and Jurkat cells) were investigated in <i>vitro via</i> EdU incorporation experiment, flow cytometry, immunofluorescence, and Western blotting. Moreover, the relationship between HOXA11-AS and miR-214-3p and between miR-214-3p, and <i>ATG12</i> was verified <i>via</i> dual-luciferase reporter assays. Our investigation demonstrated that compared to normal controls, the HOXA11-AS expression level were increased in T-ALL patients. Furthermore, in T-ALL cells, inhibition of HOXA11-AS or overexpression of miR-214-3p reduced autophagy and proliferation, while stimulating apoptosis. However, miR-214-3p inhibition counteracted HOXA11-AS-mediated suppression of T-ALL cell proliferation, autophagy, and apoptosis. In addition, HOXA11-AS modulated <i>ATG12 via</i> sponging miR-214-3p. Overall, this research indicated that lncRNA HOXA11-AS not only stimulates cell proliferation and autophagy but also inhibits apoptosis <i>via</i> the miR-214-3p/ATG12 axis, thereby suggesting that lncRNA HOXA11-AS might be a new candidate for T-ALL diagnosis and therapy.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical and histopathological changes in ovary, uterus and testicular tissues after acrylamide exposure","authors":"Hamit Uslu,&nbsp;Gözde Atila Uslu,&nbsp;Taha Abdulkadir Çoban,&nbsp;Ali Sefa Mendil,&nbsp;Emine Toraman,&nbsp;Mahmut Şahin,&nbsp;Mustafa Özkaraca","doi":"10.1007/s10735-025-10456-w","DOIUrl":"10.1007/s10735-025-10456-w","url":null,"abstract":"<div><p>Acrylamide (ACR) is a popular substance to which our exposure increases with the changes in our lifestyle and brings with it various health problems. In order to determine appropriate therapeutics against ACR damage, it is important to investigate the multiple mechanisms that may be effective in its pathophysiology. This study investigated the effects of ACR exposure on ovarian, uterine, and testicular tissues by considering different pathophysiological pathways. Male-control (MC), male-acrylamide (MACR), female-control (FC), and female-acrylamide (FACR) groups were formed. ACR was administered at a dose of 60 mg/kg for 5 days. ACR exposure decreased CAT and TrxR-specific activities, GSH levels, and Bcl-2 expression, while significantly increasing MDA, IL-6, and NFĸB p65 levels, caspase 3, and Bax expression in ovarian, uterine, and testicular tissues. Based on these results, it was determined that acrylamide induced damage in ovarian, uterine and testicular tissues through various pathways such as oxidative stress, inflammation, and apoptosis. Consequently, when selecting a therapeutic target, the substance whose efficacy is being investigated should be effective in these pathways. Furthermore, this study is the first to demonstrate the occurrence of bladder retention in both sexes following acrylamide exposure and will be an important step for future research.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circ_0008285 regulates macrophage polarization through miR-375/MAPK14 axis in sepsis-induced acute lung injury","authors":"Chen Li,&nbsp;Jianhua Liu,&nbsp;Gaixia Feng,&nbsp;Jing Su,&nbsp;Kailun Xu,&nbsp;Zhihua Zhang","doi":"10.1007/s10735-025-10465-9","DOIUrl":"10.1007/s10735-025-10465-9","url":null,"abstract":"<div><p>Acute lung injury (ALI) induced by sepsis is a serious life-threatening disease, one of its characteristics is the polarization of macrophages. Circ_0008285 has been found to be associated with various diseases. In this study, we detected the regulatory role and mechanism of circ_0008285 in sepsis-induced ALI. RAW264.7 cells treated with LPS and C57BL/6 male mice were used to construct in vitro and in vivo models, respectively. Through A series of experiments such as qRT-PCR, Western blot, CCK-8, flow cytometry, dual-luciferase reporter experiment, HE staining and TUNEL staining, the role of circ_0008285 in sepsis-induced ALI was explored. In LPS-induced RAW264.7 cell, circ_0008285 and MAPK14 were over-expressed, but miR-375 was low-expressed compared with control. The levels of IL-1β, IL-6, TNF-α, iNOS and CD86 were reduced, but CD206 and Arg1 expression were enhanced both in vitro and in vivo after knockdown of circ_0008285. In TC-1 cell co-cultured with LPS+sh-circ_0008285 cells, the viability was increased and the apoptosis level was decreased compared with LPS+sh-NC. Circ_0008285 was the sponge of miR-375, and MAPK14 was the downstream target of miR-375. The injury score, W/D ratio, MPO level and apoptosis level in lung tissue were decreased after knockdown of circ_0008285. Moreover, the total protein, neutrophils and macrophages in BALF were increased. Collectively, this study identified that circ_0008285 could sponge miR-375 to influence MAPK14 expression, and then regulate macrophage polarization of sepsis-induced ALI, which provided new insights for the treatment of sepsis-induced ALI.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carboxylesterase 1 regulates peroxisome proliferator-activated receptor gamma to inhibit the growth and metastasis of breast cancer cells","authors":"Jingli Wen,&nbsp;Lei Geng,&nbsp;Ruohan Wang,&nbsp;Xiaolei Zhang,&nbsp;Yanmin Sui,&nbsp;Xiaofang Liu,&nbsp;Xin Han","doi":"10.1007/s10735-025-10446-y","DOIUrl":"10.1007/s10735-025-10446-y","url":null,"abstract":"<div><p>Breast cancer is a common malignancy in women, and it has an absence of effective therapies. Carboxylesterase 1 (CES1), a member of the carboxylesterase family, has anti-tumor properties in several types of cancer. However, the function of CES1 in breast cancer remains unclear. Peroxisome proliferator-activated receptor gamma (PPARG) is a downstream regulator of CES1 and exhibits anti-breast cancer properties. Both CES1 and PPARG were downregulated in breast cancer tissues. Low CES1 and PPARG expression were linked to poorer breast cancer survival. We constructed CES1 knockdown and overexpression models of breast cancer cells by CES1 overexpressing plasmids and plasmids containing short hairpin RNA. High expression of CES1 inhibited breast cancer cell proliferation, evidenced by diminished cell viability, decreased DNA replication, and G1 phase arrest. CES1 overexpression decreased the protein levels of CDK2, CDK6 and cyclin B1 in breast cancer cells. CES1 inhibited the Bcl-2/Bax axis and increased Cleaved caspase-3 levels. Transwell assays showed that CES1 inhibited cell migration and invasion. CES1 increased E-cadherin protein expression and decreased Vimentin protein expression. CES1 knockdown facilitated the proliferation, migration, and invasion of breast cancer cells. CES1 was found to regulate PPARG expression in breast cancer cells positively. We transfected PPARG-interfering plasmids into breast cancer cells with CES1 overexpression. Inhibition of PPARG abrogated the anti-growth and anti-metastasis functions of CES1 in breast cancer cells. This study elucidates that CES1 inhibits the malignant progression of breast cancer by up-regulating the expression of PPARG.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-025-10446-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa-miR-194-5p regulates TRAF6-mediated M1 macrophage apoptosis in recurrent spontaneous abortion","authors":"Xin Qi,&nbsp;Yueping Ding,&nbsp;Jundi Zheng,&nbsp;Xia Geng,&nbsp;Jie Zhang,&nbsp;Yan Xu","doi":"10.1007/s10735-025-10464-w","DOIUrl":"10.1007/s10735-025-10464-w","url":null,"abstract":"<div><p>Recurrent spontaneous abortion (RSA) is linked to pro-inflammatory responses driven by macrophage M1 polarization. miR-194-5p can affect the migration and infiltration of macrophages, and significantly inhibit the release of pro-inflammatory cytokines. However, whether miR-194-5p can affect RSA through M1 macrophage-related pathway remains to be further explored. To induce human monocytic leukemia THP-1 into M1 macrophages, PMA and LPS were used. Then detect the effects of transfection with miR-194-5p mimics on the migration, invasion, cell cycle and apoptosis of M1 macrophages. Two databases, DIANA-microT and miRDB, were first used to predict the target gene of miR-194-5p, and TRAF6 was selected as the target gene of miR-194-5p, and then the binding sites of the two were predicted and verified by dual luciferase assay. Transfection of inhibitors, with or without TRAF6 siRNA (si-TRAF6), was performed on M1 macrophages to assess changes in viability, migration, aggressiveness, cell cycle, and apoptosis, as well as TRAF6, NF-κB, and Wnt5a mRNA and protein levels. Compared with the miR-NC group, transfection with the miR-194-5p mimic significantly reduced the viability, migration, and invasion abilities of M1 macrophages, arrested them in the S phase, and promoted apoptosis. miR-194-5p bound to TRAF 3’UTR-WT and reduced the viability, migration ability, and aggressiveness of M1 macrophages, increased apoptosis, and blocked the S phase. miR-194-5p negatively regulated TRAF6, resulting in decreased mRNA and protein levels of NF-κB and Wnt5a. miR-194-5p inhibitors and mimics had opposite effects, but miR-194-5p inhibitor effects could be reversed by si-TRAF6. There is a close association between RSA and M1 macrophage polarization. Furthermore, miR-194-5p inhibits the NF-κB and Wnt5a signaling pathways by negatively regulating TRAF6, thereby impeding the function of M1 macrophages and affecting the occurrence of RSA. These findings provide new therapeutic targets for the prevention, diagnosis, and treatment of RSA.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of FAM83B in pan-cancer and preliminary exploration in esophageal squamous cell carcinoma","authors":"Wei Guo,&nbsp;Xixi Zhao,&nbsp;Xinran Huang,&nbsp;Ruijuan Zhang,&nbsp;Yuchen Wang,&nbsp;Xinyu He,&nbsp;Xiangyun Ma,&nbsp;Yu Hao,&nbsp;Shangyi Geng,&nbsp;Shupei Pan,&nbsp;Hongbing Ma","doi":"10.1007/s10735-025-10452-0","DOIUrl":"10.1007/s10735-025-10452-0","url":null,"abstract":"<div><p>FAM83B is a novel oncogene that mediates transformation. Despite emerging evidence supporting an association between FAM83B and cancer, a holistic view of FAM83B’s correlation with pan-cancer is limited and its carcinogenic and radioresistant roles in esophageal squamous cell carcinoma (ESCC) remain to be explored. Using data from the TCGA project, GTEx database, and other online resources, we comprehensively examined FAM83B expression, genetic mutation, copy number variations (CNV), methylation, prognosis, function, immune-associated analyses, and drug sensitivity in pan-cancer. In addition, the biological function of FAM83B in ESCC was verified by CCK-8, colony formation assays, and flow cytometry. We discovered aberrant expression of FAM83B affected prognosis in various malignant tumors. Abnormal FAM83B mRNA expression was associated with CNV and methylation. Significant correlations were also observed between FAM83B expression and immune cell infiltration, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI) in malignancies. In vitro experiments indicated that FAM83B mRNA and protein were upregulated in ESCC, and knockdown of FAM83B significantly inhibited the proliferation while promoting apoptosis and radiosensitivity of ESCC. These results suggest the multiple functional roles of FAM83B in pan-cancer and provide an attractive diagnostic and therapeutic biomarker for certain cancer types, especially ESCC.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myoinositol improves sperm parameters in diabetic rats by reducing oxidative stress and regulating apoptosis-related genes","authors":"Mina Kiani,&nbsp;Malek Soleimani Mehranjani,&nbsp;Mohammad Ali Shariatzadeh","doi":"10.1007/s10735-025-10451-1","DOIUrl":"10.1007/s10735-025-10451-1","url":null,"abstract":"<div><p>Diabetes disrupts spermatogenesis and leads to low-quality sperm by causing oxidative stress, inducing apoptosis and reducing testosterone level. Myoinositol has antiglycemic, antioxidant, anti-apoptotic, and testosterone-regulating properties. This study aimed to evaluate the potential of myoinositol in improving sperm production and sperm quality in diabetic rats. Eighteen rats were divided into three groups (n = 6 per group): control, diabetic (Streptozotocin + Nicotinamide), and diabetic + myoinositol supplementation (300 mg/kg, for 56 days). Sperm parameters, including count, total motility, viability, and morphology, were evaluated. Additionally, several biochemical and molecular markers were measured including serum malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (TAC), testosterone, Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), and Bax/Bcl2 gene expression ratio, Bax and Bcl2 protein expression, germinal epithelium apoptosis. In the diabetic group, sperm count, viability, and normal morphology significantly decreased, along with lower levels of SOD, TAC, testosterone, FSH, and LH. Conversely, MDA levels and the Bax/Bcl2 gene ratio significantly increased compared to the control group. In the diabetic + myoinositol group, sperm count, viability, morphology, and motility significantly improved (P &lt; 0.001), as did TAC, testosterone, and FSH levels (P &lt; 0.001), with a significant increase in LH levels (P &lt; 0.05). Additionally, MDA levels (P &lt; 0.01) and the Bax/Bcl2 gene ratio (P &lt; 0.05) were significantly reduced compared to the diabetic group. This study showed that diabetes impairs sperm quality, antioxidant capacity, and hormones while increasing oxidative stress and apoptosis. Myoinositol improves sperm parameters, boosts antioxidants, and reduces apoptosis, suggesting its therapeutic potential for diabetes-induced reproductive dysfunction.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cell exosomes regulate TGFβ/Smad3 by decreasing the METTL3-NEAT1 axis to inhibit scar progression after breast surgery","authors":"Juan Du,&nbsp;Jincheng Wu,&nbsp;Qinqin Song,&nbsp;Shuangru Li,&nbsp;Youwang Hong,&nbsp;Aizaz Anwar,&nbsp;Quanyou Fu,&nbsp;Jisong Liu","doi":"10.1007/s10735-025-10441-3","DOIUrl":"10.1007/s10735-025-10441-3","url":null,"abstract":"<div><h3>Background</h3><p>Scars are traces of tissue loss left behind by connective tissue overgrowth and repair. Studies in recent years have shown that mesenchymal stem cell exosomes (MSC-Exo) have the ability to inhibit and repair cutaneous scarring, but their specific role in post-breast surgery scar formation and the mechanisms behind it remain enigmatic.</p><h3>Methods</h3><p>Extraction and characterization of exosomes from mesenchymal stem cells (MSCs). Western Blot and RT-qPCR were used to evaluate the expression of fibrillar protein and TGF-β/Smad3 in mammary hypertrophic scar fibroblasts (MHSFs) stimulated with MSC-Exo, sh-METTL3, sh-NEAT1 and their negative controls. Construction of a mouse model of proliferative scar formation using mechanical tension and detection of fibronectin and pathway protein expression using Western Blot and RT-qPCR. Pathologic changes of mammary scarring in mice using HE staining, Masson staining and immunofluorescence.</p><h3>Results</h3><p>Both in vitro and in vivo, MSC-Exo, sh-METTL3 and sh-NEAT1 were shown to decrease the expression of COL1A1, COL3A1, α-SMA, fibronectin, TGF-β, p-Smad2/Smad2, p-Smad3/Smad3, by Western Blot and RT-qPCR. In addition, improved lesions and reduced collagen deposition were observed in mice by HE and Masson assays.</p><h3>Conclusions</h3><p>In summary, our study revealed that exosomes of MSCs function through the m6A methyltransferase METTL3, which regulates the NEAT1/TGF-β/Smad3 axis to slow down the rate of scar formation after breast surgery.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}