Experimental cell research最新文献

{"title":"Long noncoding RNA ZRANB2-AS2 promotes endothelial cell dysfunction by inhibiting phosphorylation of acetyl-CoA carboxylase 1 in diabetes","authors":"Tianchi Chen ,&nbsp;Bing Wang ,&nbsp;Donglin Li ,&nbsp;Xinyu Yu ,&nbsp;Kejia Lv ,&nbsp;Qianqian Zhu ,&nbsp;Chenyang Qiu ,&nbsp;Yangyan He ,&nbsp;Hongkun Zhang ,&nbsp;Ziheng Wu","doi":"10.1016/j.yexcr.2025.114572","DOIUrl":"10.1016/j.yexcr.2025.114572","url":null,"abstract":"<div><div>LncRNA has been implicated in the regulation of diabetes. We identified a novel lncRNA that inhibits phosphorylation of acetyl-CoA carboxylase 1 to modulate the dysfunction of vascular endothelial cells under high glucose conditions. In vitro experiments were performed to investigate the effects of lnc RNA ZRANB2-AS2 on ACC1 phosphorylation, free fatty acid and triglyceride levels, angiogenesis, cell apoptosis, cell proliferation and migration rate. Further, in vivo experiments were designed to examine the effects of lnc RNA ZRANB2-AS2 on the level of ACC1, the limb ischemia and foot movement of mice, as well as on apoptosis, cell proliferation, and migration of vascular endothelial cells under conditions of high glucose.By RNA sequencing, we identified a lncRNA, ZRANB2-AS2, which is highly expressed in human umbilical vein endothelial cells (HUVECs) under high glucose condition. We demonstrated that it could promote apoptosis and inhibit angiogenesis, proliferation and migration of endothelial cells. Using RNA pull-down and RIP assays, the binding specificity of lncRNA ZRANB2-AS2 and acetyl-CoA carboxylase 1(ACC1) was determined. We further established the rescue assay by adding CMS-121, a specific ACC1 inhibitor. These findings suggested that CMS-121 could reverse the inhibition of lncRNA ZRANB2-AS2 on ACC1 phosphorylation, decrease intracellular free fatty acid and triglyceride levels. We conducted in vivo experiments to determine the inhibitory effect of lncRNA ZRANB2-AS2 in diabetic mice model. Lnc ZRANB2-AS2 inhibits cell proliferation, migration and angiogenesis while accelerates apoptosis of endothelial cells by regulating the phosphorylation of acetyl-CoA carboxylase 1 in diabetes.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 2","pages":"Article 114572"},"PeriodicalIF":3.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873471","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}

{"title":"Identification and validation of SLC16A8 as a prognostic biomarker in clear cell renal cell carcinoma: a six-gene solute carrier signature","authors":"Hantao Wen ,&nbsp;Fang Dai ,&nbsp;Huming Wang ,&nbsp;Yu Lin ,&nbsp;Zihan Xu ,&nbsp;Zhaojie Lyu Ph.D","doi":"10.1016/j.yexcr.2025.114567","DOIUrl":"10.1016/j.yexcr.2025.114567","url":null,"abstract":"<div><div>Solute carrier (SLC) proteins are essential for nutrient transport, influencing tumor metabolism and growth while preserving cellular homeostasis. Despite the critical biological functions of these transporters, their applicability as therapeutic targets in clear cell renal cell carcinoma (ccRCC) remains largely unexplored. In the current study, we analyzed transcriptomic data and discovered 77 differentially expressed SLC genes in ccRCC, with 24 demonstrating predictive potential. Using Lasso regression, we developed a prognostic signature comprising six key genes: SLC2A3, SLC11A1, SLC14A1, SLC16A8, SLC22A6, and SLC28A1. This signature demonstrated strong diagnostic performance and served as an independent predictor of patient survival. Further analysis integrating clinical variables and risk scores enabled the construction of nomograms, which exhibited high predictive accuracy for patient outcomes. Immune profiling revealed distinct infiltration patterns between risk groups: high-risk patients showed elevated levels of memory B cells, activated CD4⁺ T cells, regulatory T cells (Tregs), M0 macrophages, and neutrophils. In contrast, their low-risk counterparts showed M1 macrophages, resting dendritic cells, and resting mast cells. Validation experiments confirmed that SLC16A8 was significantly overexpressed in ccRCC tissues compared to normal samples, correlating with poor prognosis. Functional studies demonstrated that SLC16A8 knockdown impaired tumor progression in vitro. Consistent with these findings, in vivo experiments demonstrated reduced tumor growth upon SLC16A8 knockdown. Mechanistically, decreased SLC16A8 attenuated PI3K/AKT signaling, suggesting a potential regulatory pathway in ccRCC progression. In summary, we established a six-gene SLC signature with significant prognostic value in ccRCC. Among these genes, SLC16A8 emerged as a promising biomarker and therapeutic target, warranting further investigation.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 2","pages":"Article 114567"},"PeriodicalIF":3.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855923","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}

{"title":"Biomarkers for the detection of circulating tumor cells","authors":"Karol Gostomczyk ,&nbsp;Magdalena Drozd ,&nbsp;Mohammed Dheyaa Marsool Marsool ,&nbsp;Anju Pandey ,&nbsp;Khachirha Tugas ,&nbsp;Jose Chacon ,&nbsp;Hamnah Tayyab ,&nbsp;Ashraf Ullah ,&nbsp;Jędrzej Borowczak ,&nbsp;Łukasz Szylberg","doi":"10.1016/j.yexcr.2025.114555","DOIUrl":"10.1016/j.yexcr.2025.114555","url":null,"abstract":"<div><div>Circulating tumor cells (CTCs) have emerged as a key biomarker in cancer detection and prognosis, and their molecular profiling is gaining importance in precision oncology. Liquid biopsies, which allow the extraction of CTCs, circulating tumor DNA (ctDNA) or cell-free DNA (cfDNA), have measurable advantages over traditional tissue biopsies, especially when molecular material is difficult to obtain. However, this method is not without limitations. Difficulties in differentiating between primary and metastatic lesions, uncertain predictive values and the complexity of the biomarkers used can prove challenging. Recently, high cell heterogeneity has been identified as the main obstacle to achieving high diagnostic accuracy. Because not all cells undergo epithelial-mesenchymal transition (EMT) at the same time, there is a large population of hybrid CTCs that express both epithelial and mesenchymal markers. Since traditional diagnostic tools primarily detect epithelial markers, they are often unable to detect cells with a hybrid phenotype; therefore, additional markers may be required to avoid false negatives. In this review, we summarize recent reports on emerging CTCs markers, with particular emphasis on their use in cancer diagnosis. Most of them, including vimentin, TWIST1, SNAI1, ZEB1, cadherins, CD44, TGM2, PD-L1 and GATA, hold promise for the detection of CTCs, but are also implicated in cancer progression, metastasis, and therapeutic resistance. Therefore, understanding the nature and drivers of epithelial-mesenchymal plasticity (EMP) is critical to advancing our knowledge in this field.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 1","pages":"Article 114555"},"PeriodicalIF":3.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828291","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}

{"title":"Potential role of Sigma-1 receptor inhibition and ER stress-related pathways in upregulating definitive endoderm markers in human embryonic stem cells","authors":"Elmira Rezaei Zonooz ,&nbsp;Zahra Ghezelayagh ,&nbsp;Azadeh Moradmand ,&nbsp;Hamid Reza Aghayan ,&nbsp;Faezeh Shekari ,&nbsp;Yaser Tahamtani","doi":"10.1016/j.yexcr.2025.114557","DOIUrl":"10.1016/j.yexcr.2025.114557","url":null,"abstract":"<div><div>Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) participate in stem cell proliferation, differentiation, and apoptosis. Sigma-1 receptor (S1R) is a unique ER chaperon protein that regulates ER stress and UPR. Here, we examine the effects of S1R inhibition on pluripotency and differentiation of human embryonic stem cells (hESCs). hESCs were treated with different doses of an S1R inhibitor (BD 1047), and we investigated the expressions of different pluripotency and lineage-specific genes. The BD-treated hESCs showed increased SRY-box transcription factor 17 (SOX17) expression [definitive endoderm-specific protein], and reductions in NANOG expression and in the number of alkaline phosphatase (ALP)-positive colonies. In silico gene expression analysis of three datasets that contained the hESCs-derived DE samples (GSE98324, GSE63592, GSE52658) was performed to investigate the ER stress-related gene expression patterns during DE differentiation. In silico analysis revealed that UPR-related genes upregulated during DE differentiation and <em>CCL2</em> was the only gene present in all three DE datasets. qRT-PCR and immunostaining showed that <em>CCL2</em>, <em>eIF2A</em>, <em>ATF4</em>, <em>XBP1</em>, <em>GRP78</em>, <em>DDIT3</em>, <em>DNAJB9,</em> and <em>PDIA5</em> which are UPR related marker genes were all upregulated in both the BD-treated hESCs and female and male hESC-derived DE cells. The results of this study suggest possible roles for S1R, ER stress-related genes, and the CCL2 pathway during differentiation of hESCs into DE. These potential new targets may improve the efficiency of protocols used to differentiate endodermal lineages.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 2","pages":"Article 114557"},"PeriodicalIF":3.3,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863418","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}

{"title":"Type III sodium-dependent inorganic phosphate transporters are required for the phenotypes in human brain microvascular endothelial cells","authors":"Kazuki Ohuchi ,&nbsp;Ku Watanabe ,&nbsp;Mutsuko Izutsu ,&nbsp;Ayane Mishima ,&nbsp;Junya Murata ,&nbsp;Hisaka Kurita ,&nbsp;Isao Hozumi ,&nbsp;Yuichi Hayashi ,&nbsp;Masatoshi Inden","doi":"10.1016/j.yexcr.2025.114556","DOIUrl":"10.1016/j.yexcr.2025.114556","url":null,"abstract":"<div><div>Inorganic phosphate (Pi) homeostasis in the brain is critical for the development of primary brain calcification (PBC). In the brains of patients with PBC, calcification occurs in the cerebral small vessels, and it is primarily caused by mutated <em>SLC20A2</em>, a gene that encodes a type III Pi transporter. A previous study founded that the SLC20 family, which includes SLC20A1 and SLC20A2, contributes to Pi homeostasis in the central nervous system. However, the impact of these Pi transporters on the brain vessel phenotype remains unknown. Thus, in this study, we aimed to investigate the effect of SLC20A1 or SLC20A2 depletion on the phenotype of human brain microvascular endothelial cells (hBMECs). We assessed the primary phenotypes of vascular endothelial cells, such as proliferation, tube formation, and VE-cadherin expression. The results showed that hBMECs silenced for SLC20A1 or SLC20A2 had decreased proliferative and angiogenic ability, as well as VE-cadherin expression. The intracellular Pi concentration ([Pi]_i) remained constant in SLC20A1-silenced hBMECs whereas it increased in SLC20A2-silenced cells. Tube formation ability was no change even at 3 mM, a concentration higher than [Pi]_i which was increased in SLC20A2-silenced hBMECs. Thus, increased [Pi]_i in SLC20A2-silenced hBMECs may have a small impact on phenotypic changes. In conclusion, abnormalities in Pi homeostasis caused by SLC20A2 depletion were suggested to play a minor role in PBC endothelial pathology.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 1","pages":"Article 114556"},"PeriodicalIF":3.3,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824216","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}

{"title":"USP28 knockdown and small molecule inhibitors promote KRT1 destabilization and sensitize hepatocellular carcinoma cells to sorafenib","authors":"Zilin Li ,&nbsp;Yan Wang ,&nbsp;Jiahui Hu ,&nbsp;Jingyang Du ,&nbsp;Huizong Nie ,&nbsp;Yiling Xi ,&nbsp;Yue Huang ,&nbsp;Kexin Wang ,&nbsp;Kaixuan Zhang ,&nbsp;Qiuran Xu ,&nbsp;Liyan Cheng ,&nbsp;Dongsheng Huang ,&nbsp;Linglan Tu","doi":"10.1016/j.yexcr.2025.114558","DOIUrl":"10.1016/j.yexcr.2025.114558","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) is a significant malignant tumor that is typically diagnosed late and has a poor prognosis. USP28 (Ubiquitin-specific protease 28), a deubiquitinating enzyme within the ubiquitin-specific proteases (USPs) family, plays a pivotal role in various biological processes, especially in cancer progression. However, its functions and molecular mechanisms in HCC are still unknown.</div></div><div><h3>Methods</h3><div>We first analyzed the expression level of USP28 in HCC tissues relative to normal tissues using TCGA database. This was further validated by qRT-PCR and Western Blot. To investigate the function of USP28 in HCC, CCK-8 assay, clone formation assay and Transwell assay were performed in control and USP28 knockdown or overexpressed HCC cells. To explore potential downstream targets of USP28, we used IP-MS analysis. The interaction between USP28 and KRT1 was confirmed by immunoprecipitation and immunofluorescence staining. Finally, we evaluated the in vivo effects of USP28 on HCC growth and metastasis using a ectopic tumor-bearing mouse model.</div></div><div><h3>Results</h3><div>The expression of USP28 in HCC tissues was significantly higher than that in normal tissues, and its high expression was associated with poor prognosis. Functional experiments showed that down-regulation of USP28 expression effectively inhibited the proliferation, migration and invasion of HCC cells, while overexpression of USP28 produced the opposite effect. Mechanistic investigations demonstrated that USP28 interacted with KRT1 and exerted deubiquitination on KRT1, thereby maintaining the stability of KRT1. Further studies revealed that USP28 knockdown resulted in decreased IFITM3 expression, which inhibited HCC cell proliferation. In addition, USP28 knockdown combined with sorafenib inhibited tumor growth and metastasis in tumor xenograft mice model.</div></div><div><h3>Conclusions</h3><div>Our study confirmed the carcinogenic effects of USP28 by stabilizing KRT1 expression and promoting IFITM3. USP28 small molecule inhibitors can inhibit the proliferation of hepatocellular carcinoma cells and enhance the sensitivity of hepatocellular carcinoma cell lines to sorafenib. This provides a theoretical basis for USP28 to be a new clinical method to alleviate sorafenib resistance.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 2","pages":"Article 114558"},"PeriodicalIF":3.3,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848481","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}

{"title":"Repositioning antimalarial drugs as anticancer agents: focus on Tafenoquine","authors":"Christopher E. Barton,&nbsp;Bailey Blair,&nbsp;Libby Godo,&nbsp;Anna Gray,&nbsp;Lydia Heron-Goar,&nbsp;Holly Hill,&nbsp;Amanda Long,&nbsp;Hannah Moore,&nbsp;Rylee Rickett,&nbsp;Sandra Tomas","doi":"10.1016/j.yexcr.2025.114551","DOIUrl":"10.1016/j.yexcr.2025.114551","url":null,"abstract":"<div><div>Due to the expensive and lengthy process of drug design and approval, drug repurposing (or repositioning) has become another option for identifying preexisting molecules that may be used for alternative purposes. Recently, some antimalarial compounds have been shown to display efficacy against cancer cell proliferation. In this study, we provide evidence to suggest that multiple preexisting antimalarial drugs can reduce the viability of human cancer cells in culture. Furthermore, we provide the first evidence that one antimalarial, Tafenoquine (LD₅₀ = 9.6 μM in HCT116 cells), is capable of decreasing viability with an efficacy comparable to Etoposide (LD₅₀ = 15.2 μM in HCT116 cells) Further, Tafenoquine induces apoptosis and increases the expression of genes involved in cell cycle arrest and cell death. We also show that cells are sensitized to the apoptotic effects of Tafenoquine following depletion of the heme oxygenase 1 (HMOX-1) gene. Collectively, our studies confirm that antimalarial compounds hold the potential for use as anticancer agents and provide the first evidence to detail the potent efficacy of Tafenoquine against cancer cells in culture.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 2","pages":"Article 114551"},"PeriodicalIF":3.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859316","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}

{"title":"Creation of a rat model of ovarian endometriosis: a novel and easy approach to simulating chocolate cysts","authors":"Weisen Fan ,&nbsp;Yingjie zhang ,&nbsp;Yuanquan Dai ,&nbsp;Haotian Ma ,&nbsp;Ruihua Zhao ,&nbsp;Yong Liu","doi":"10.1016/j.yexcr.2025.114553","DOIUrl":"10.1016/j.yexcr.2025.114553","url":null,"abstract":"<div><div>Ovarian endometriosis(OEM) is the most common type of endometriosis, but there is still a lack of simple and easy-to-promote animal models. Therefore, it is necessary to establish a feasible animal model of OEM and analyze its pathogenesis. In this study, a novel insertional surgical method was used to construct the OEM rat model. The rat model group's morphology and HE staining revealed a close relationship between the transplanted ectopic tissue and the ovary. Compared to the surgery group and the normal group, the bilateral OEM group's level of Anti-mullerian hormone(AMH) was noticeably lower. There was no discernible difference in the unilateral OEM group's AMH level between the normal and sham operation groups. Serum interleukin-1beta(IL-1β) levels in four groups of rats showed bilateral OEM had the greatest level, followed by unilateral OEM. Compared to the normal group, the two model groups had greater serum levels of IL-1β. According to immunohistochemistry, unilateral OEM had higher Intercellular adhesion molecule 1(ICAM1), Matrix metalloproteinase-9(MMP9), Tumor necrosis factor-α(TNF-a), and IL-1β expression levels than the normal rat endometrium. WB revealed that bilateral and unilateral ectopic tissues had higher levels of MMP9, TNF-a, Vascular endothelial growth factor D and IL-1β expression than normal tissues. Transcriptome research revealed that ectopic tissues had higher pro-inflammatory, immunological, and ectopic endometrial proliferation pathways than normal tissues. The ovaries of unilateral OEM have down-regulated immune and inflammation-related pathways and up-regulated steroid hormones compared to normal ovarian tissue. GSEA enrichment analysis comparisons between rat and human endometriotic tissue revealed that Janus kinase-signal transducer and activator of transcription(JAK-STAT), Nuclear factor-kappa B(NFκB), and Toll-like receptors were up-regulated. The intercalation approach of OEM building used in this work is more akin to the human OEM lesion type. It deserves promotion that modeling is more straightforward and has a higher success rate than the suture approach.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 1","pages":"Article 114553"},"PeriodicalIF":3.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824215","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}

{"title":"Evaluation of the impact of miR-3143 on the PI3K/AKT signaling pathway and its subsequent influence on the metastatic phenotype of triple-negative breast cancer cells","authors":"Yalda Khazaei-Poul ,&nbsp;Ali Ahmadizad Firouzjaei ,&nbsp;Mahdi Paryan ,&nbsp;Ali Tafti ,&nbsp;Samira Mohammadi-Yeganeh","doi":"10.1016/j.yexcr.2025.114552","DOIUrl":"10.1016/j.yexcr.2025.114552","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are recognized to have a pivotal role in the progression and metastatic dissemination encompassing diverse cancer varieties, such as triple-negative breast cancer (TNBC). Recent evidence has suggested that specific miRNA species can directly or indirectly influence the onset, progression, and relapse of TNBC. Previous studies have reported the frequent reduction of miR-3143 in TNBC, which appears to coincide with the activation of proliferative signaling pathways. However, the potential restorative effects of miR-3143 on TNBC cellular behavior remain unexplored. In the present study, we utilized exosome-mediated delivery to introduce miR-3143 into TNBC cells and investigated its impact on the PI3K/AKT pathway and the resulting effects on cellular proliferation, movement, and apoptosis. MDA-MB-231 TNBC cells underwent treatment with miR-3143-electroporated human umbilical cord mesenchymal stem cell (HUCMSC)-derived exosomes. RT-qPCR analysis was utilized to assess the influence of miR-3143 overexpression on the expression of its target genes, PIK3CA and AKT1, which was further validated through dual-luciferase reporter assays. Our results demonstrated that the overexpression of miR-3143 could effectively decline the level of AKT1 and PIK3CA by directly binding to their 3′-UTRs. Furthermore, the introduction of miR-3143 into TNBC cells resulted in a significant enhancement of apoptotic activities. Interestingly, the delivery of miR-3143 via HUCMSC-derived exosomes could inhibit the protumorigenic and prometastatic behaviors of TNBC cells, potentially limiting their malignant progression. Collectively, these findings enhance comprehension of the regulatory mechanisms by which miR-3143 can modulate the metastatic potential of TNBC cells. The insights gained from this study may facilitate the creation of innovative miRNA-targeting approaches to combat the aggressive nature of TNBC andstrengthen treatment effectiveness.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 1","pages":"Article 114552"},"PeriodicalIF":3.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824218","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}

{"title":"CircBRWD1 promotes hepatitis B virus replication and hepatocellular carcinoma progression by regulating the miR-513a-5p/TNPO1 axis","authors":"Jiabao Geng ,&nbsp;Fei Huang ,&nbsp;Qiannan Liu ,&nbsp;Bingji Wang ,&nbsp;Xi Xiong ,&nbsp;Shouming Wang ,&nbsp;Yuan Dong ,&nbsp;Yuecheng Yu ,&nbsp;Weifeng Zhao","doi":"10.1016/j.yexcr.2025.114554","DOIUrl":"10.1016/j.yexcr.2025.114554","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC), primarily caused by chronic hepatitis B virus (HBV) infection, remains a leading cause of liver cancer worldwide. Despite advances in antiviral therapies, persistent HBV replication, mediated by covalently closed circular DNA (cccDNA), contributes to poor prognoses and frequent recurrence of HCC. This study investigates for the first time the role of circular RNA circBRWD1 in HBV-related HCC, aiming to elucidate its function and regulatory mechanism in HBV replication and hepatocarcinogenesis. Results showed that circBRWD1 was significantly overexpressed in HBV-positive HCC tissues and cell lines compared to HBV-negative controls and promoted HBV replication by increasing cccDNA accumulation. Silencing circBRWD1 markedly reduced the levels of HBV DNA, HBV surface antigen (HBsAg), HBV e antigen (HBeAg), and HBV core antigen (HBcAg), indicating its critical role in HBV replication. Functionally, circBRWD1 knockdown led to reduced cell proliferation, colony formation, and migration while increasing apoptosis in HCC cells. Mechanistic studies revealed that circBRWD1 acts as a sponge for miR-513a-5p, thereby upregulating TNPO1, a key player in promoting HCC malignancy. Rescue experiments confirmed that TNPO1 overexpression reversed the effects of circBRWD1 depletion, restoring cell proliferation, migration, and HBV replication. Additionally, circBRWD1 depletion significantly reduced tumor growth with reduced expression of TNPO1 and increased miR-513a-5p levels in a mouse xenograft model. Collectively, this study identifies circBRWD1 as a key oncogenic circRNA that facilitates HBV replication and HCC progression via the miR-513a-5p/TNPO1 axis. Targeting circBRWD1 may offer a novel therapeutic strategy for HBV-related HCC, potentially addressing the challenge of HBV persistence and improving patient outcomes.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 2","pages":"Article 114554"},"PeriodicalIF":3.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859315","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}