JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Kindlin-3 Promotes Angiogenesis via Notch Signalling and Is Crucial for Functional Recovery Postmyocardial Infarction","authors":"Yan Sun,&nbsp;Wei Zheng,&nbsp;Xianling Liu,&nbsp;Kai Wang,&nbsp;Di Xu","doi":"10.1111/jcmm.70494","DOIUrl":"https://doi.org/10.1111/jcmm.70494","url":null,"abstract":"<p>Angiogenesis is crucial for minimising ischemic injury postmyocardial infarction (MI), making it a significant target for cardioprotective therapies. While Kindlin-3 has been linked to angiogenesis in breast cancer, its specific function in the context of MI remains largely unexplored. Although Kindlin-3 has been implicated in breast cancer-related angiogenesis, its role in MI remains underexplored. This study investigates the role of Kindlin-3 in promoting angiogenesis, a process critical for cardiac recovery following MI. The study demonstrated a significant upregulation of Kindlin-3 in cardiac microvascular endothelial cells (CMECs) in mice post-MI. Overexpression of Kindlin-3, achieved through cardiotropic adeno-associated virus serotype 9 (AAV9) with the endothelial-specific promoter Tie2, enhanced myocardial angiogenesis, improved cardiac function, decreased cardiomyocyte apoptosis and reduced fibrosis. In vitro, Kindlin-3 overexpression promoted CMECs proliferation, migration, tube formation and the expression of angiogenesis-related genes. Conversely, Kindlin-3 knockdown exerted opposite effects. Mechanistically, Kindlin-3 activated the Notch signalling pathway, as its effects were abrogated by the Notch inhibitor DAPT and β1 integrin knockdown. This study identifies Kindlin-3 as a novel enhancer of angiogenesis and suggests its potential as a therapeutic target for myocardial repair.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70494","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of the Hub Gene LDB3 in Stanford Type A Aortic Dissection Based on Comprehensive Bioinformatics Analysis","authors":"Xinyi Liu,&nbsp;Xing Liu,&nbsp;Bin Wan,&nbsp;Yipeng Ge,&nbsp;Haiou Hu,&nbsp;Hong Yu,&nbsp;Meng Zhao,&nbsp;Huadong Li,&nbsp;Junming Zhu","doi":"10.1111/jcmm.70471","DOIUrl":"https://doi.org/10.1111/jcmm.70471","url":null,"abstract":"<p>Stanford type A aortic dissection (TAAD) is a life-threatening disease. This study explored the role of LIM domain binding 3 (LDB3) in TAAD progression. Four datasets from the Gene Expression Omnibus were analyzed to identify TAAD-related hub genes. LDB3 single nucleotide polymorphisms (SNPs) were assessed in the UK Biobank. Western blotting and immunofluorescence detected LDB3 expression in angiotensin II (Ang II) stimulated human aortic vascular smooth muscle cells (HA-VSMC), human samples, and a murine model. Bioinformatics identified tissue inhibitor of metalloproteinase-1 (TIMP1) and LDB3 as TAAD hub genes. TIMP1 was expressed in macrophages, mesenchymal cells, and smooth muscle cells, while LDB3 was mostly expressed in smooth muscle cells. Validation showed TIMP1 was upregulated and LDB3 downregulated in TAAD. Six LDB3 SNPs were associated with aortic aneurysm and dissection in the UK Biobank. In human and murine samples, LDB3 expression was reduced in diseased tissues and co-localized with smooth muscle. Ang II-stimulated HA-VSMC exhibited LDB3 reduction and altered intercellular connections. The aforementioned findings suggest that the newly identified gene LDB3 is crucial in the progression of TAAD.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidation of Dexmedetomidine-Induced Analgesic Tolerance Mechanisms in Neuropathic Pain With Modulation of SGK1, NR2A, and NR2B Expression via the Spinal SGK1/NF-κB Signalling Pathway","authors":"Wang Huikang,&nbsp;Cao Shiya,&nbsp;Pan Di,&nbsp;Faisal Ayub Kiani,&nbsp;Li Hao,&nbsp;Nan Sha,&nbsp;Lin Xuan,&nbsp;Mahmoud M. Abouelfetouh,&nbsp;Zulfiqar Ahmed,&nbsp;Ding Mingxing,&nbsp;Ding Yi","doi":"10.1111/jcmm.70372","DOIUrl":"https://doi.org/10.1111/jcmm.70372","url":null,"abstract":"<p>Neuropathic pain (NP), resulting from nerve damage, is difficult to manage and often requires long-term treatment. However, prolonged use of pain medications can lead to addiction and reduced effectiveness over time. Understanding drug tolerance is essential for developing improved pain management strategies. Dexmedetomidine (DEX) is effective in targeting the <i>α2</i>-adrenergic receptor, providing relief from pain, especially NP. However, its extended use leads to tolerance and hinders its clinical utility. Herein, we investigated tolerance mechanisms and potential applications of this drug in managing NP. Adult C57BL/6 mice (male) were distributed into DEX Dosage Groups (<i>n</i> = 48), DEX Tolerance Model Groups (<i>n</i> = 32), <i>SGK1</i> Inhibitor GSK650394 Groups (<i>n</i> = 48), and <i>NF</i>-<i>κB</i> Inhibitor PDTC Groups (<i>n</i> = 32) to explore dexmedetomidine's effects on NP and tolerance mechanisms. NP was established via selective ligation of the sciatic nerve branch (SNI), followed by administration of DEX. The results revealed a dose-dependent analgesic effect of DEX, with significant increases in pain thresholds observed compared to the sham group (<i>p</i> &lt; 0.05). Optimal efficacy was found at a dose of 30 μg/kg, indicating its potential as an effective treatment for NP (<i>p</i> &lt; 0.05). However, continuous administration of DEX over 13 days induced analgesic tolerance, evidenced by an initial increase in pain thresholds followed by a gradual decrease (<i>p</i> &lt; 0.05). Despite an initial efficacy in elevating pain thresholds, the analgesic effect of DEX diminished over time, returning to pre-dose levels after 5 days (<i>p</i> &lt; 0.05). Transcriptome sequencing of spinal cord samples from mice receiving multiple DEX injections revealed differential gene expression patterns, notably upregulation of <i>SGK1</i>, <i>NR2A</i>, and <i>NR2B</i> subunits (<i>p</i> &lt; 0.05). Inhibiting <i>SGK1</i> mitigated DEX-induced tolerance, suggesting its involvement in tolerance development (<i>p</i> &lt; 0.05). Moreover, <i>NF</i>-<i>κB</i> inhibition reversed DEX-induced tolerance and implicated the <i>SGK1</i>-<i>NF</i>-<i>κB</i> pathway in the mediation of analgesic tolerance. To sum up, these findings revealed the molecular mechanism underlying DEX-induced analgesic tolerance in the NP model and offer potential avenues for future therapeutic interventions.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HOGA1 Suppresses Renal Cell Carcinoma Growth via Inhibiting the Wnt/β-Catenin Signalling Pathway","authors":"Congmin Wang,&nbsp;Yu Liu,&nbsp;Ying Tan,&nbsp;Fuyi Xu,&nbsp;Mingyao Wang,&nbsp;Yiming Tang,&nbsp;Guofeng Nie,&nbsp;Xiaodong Chi,&nbsp;Zhaowei Xu,&nbsp;Yuxue Xu,&nbsp;Baijiao An,&nbsp;Geng Tian,&nbsp;Donglai Qi,&nbsp;Cuifang Yao","doi":"10.1111/jcmm.70490","DOIUrl":"https://doi.org/10.1111/jcmm.70490","url":null,"abstract":"<p>Changes in hydroxyproline metabolism are reported to promote tumorigenesis. HOGA1 is a useful marker for diagnosing primary hyperoxaluria 3, catalysing the final step of mitochondrial hydroxyproline metabolism from 4-hydroxy-2-oxoglutarate (HOG) to glyoxylate and pyruvate; however, its specific mechanism in RCC remains unclear. This study investigated the role of HOGA1 in the pathogenesis of ccRCC. The results showed that HOGA1 was decreased significantly in tumour tissues, with this low expression associated with a poor prognosis in patients with ccRCC. QTL mapping showed that <i>Hoga1</i> was <i>cis</i>-regulated. Gene enrichment analyses showed that <i>Hoga1</i> co-expressed genes were enriched in the Wnt/β-catenin signalling pathway. Furthermore, in vitro and in vivo assays demonstrated that HOGA1 significantly inhibited the proliferation, invasion and migration of renal carcinoma cells via the Wnt/β-catenin–c-Myc/CyclinD1 axis, probably via regulating the level of HOG. In conclusion, this study demonstrates that HOGA1 has a tumour suppressor role by inhibiting the Wnt/β-catenin signalling pathway. This finding provides new insights into the function of HOGA1 in ccRCC.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70490","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting PKC as a Therapeutic Strategy to Overcome Chemoresistance in TNBC by Restoring Aurora Kinase B Expression","authors":"Bing Cheng,&nbsp;Jinxin Chen,&nbsp;Vera Katalina,&nbsp;Guojie Long,&nbsp;Chaoying Wei,&nbsp;Zhitong Niu,&nbsp;Chen Chen,&nbsp;Panpan Wang,&nbsp;Qiang Yu,&nbsp;Wenyu Wang","doi":"10.1111/jcmm.70464","DOIUrl":"https://doi.org/10.1111/jcmm.70464","url":null,"abstract":"<p>Triple-negative breast cancer (TNBC) poses a significant challenge due to its high mortality rates, primarily attributed to resistance against chemotherapy regimens containing taxanes like paclitaxel. Thus, developing combinatorial strategies to override resistance is a pressing need. By taking advantage of a library screening with various kinase inhibitors, we found that the small-molecule inhibitor enzastaurin targeting protein kinase C (PKC) could overcome resistance in TNBC cells. Mechanistically, dual treatment with paclitaxel and enzastaurin resulted in efficient mitotic arrest and subsequent cell death by restoring AURKB expression. Further analysis revealed that the GCN2-p-eIF2α axis was responsible for the posttranscriptional accumulation of AURKB upon combinatorial treatment. Finally, we confirmed that combinatorial regimens synergistically suppressed tumour growth in vivo in mouse models. Moreover, the efficiency of dual treatment was largely determined by AURKB, implying that AURKB could be a potential predictive marker for stratifying patients who may benefit from the combinatorial treatment. Collectively, our study not only unravels a novel underlying mechanism for paclitaxel resistance in TNBC but also provides a new potential combinatorial therapeutic strategy in the clinic.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa_circ_0004662 Accelerates the Progression of Ulcerative Colitis via the microRNA-532/HMGB3 Signalling Axis","authors":"Chunhua Qiu,&nbsp;Yun Chen,&nbsp;Huan Xia,&nbsp;Jun Duan,&nbsp;Lu Zhang,&nbsp;You Zhang,&nbsp;Ziyang Chen,&nbsp;Li Zhang","doi":"10.1111/jcmm.70430","DOIUrl":"https://doi.org/10.1111/jcmm.70430","url":null,"abstract":"<p>Increasing research has indicated that circular RNAs (circRNAs) are crucial for the development of ulcerative colitis (UC). Thus, we attempted to identify the role of hsa_circ_0004662 in UC progression. Hsa_circ_0004662 expression was determined via qRT-PCR. Lipopolysaccharide (LPS)-induced inflammation in normal colonic epithelial cells (ECs). The hsa_circ_0004662 content was then assessed in a mucosal inflammatory bowel disease (IBD) model. Cell proliferation was examined via CCK-8 and EdU uptake assays. Apoptotic rates were analysed via flow cytometry. The protein content was quantified via Western blotting. Enzyme-linked immunosorbent assay kits were used to detect IL-1β, TNF-α and IL-6, and dual-luciferase reporter (DLR) assays were used to identify interactions between miR-532 and circ_0004662 or HMGB3. An animal model of UC was also developed for confirmation. In this study, we identified the function of hsa_circ_0004662 in promoting UC progression. Hsa_circ_0004662 was upregulated in clinical UC tissues and LPS-induced colonic ECs, and its knockdown inhibited apoptosis, reduced inflammatory cytokine release and promoted cell proliferation in vitro. Mechanistically, hsa_circ_0004662 acted as a molecular sponge for miR-532, which targets HMGB3. The hsa_circ_0004662/miR-532/HMGB3 axis was further validated in a DSS-induced colitis mouse model, where hsa_circ_0004662 knockdown attenuated inflammation and tissue damage. These findings suggested that hsa_circ_0004662 contributes to UC progression through the miR-532/HMGB3 signalling pathway, offering potential targets for UC therapy.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70430","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Disulfide Isomerase Involvement in Dilated Cardiomyopathy Caused by Filamin C Deficiency in Male Mice","authors":"He Xuan,&nbsp;Chenghao Fan,&nbsp;Xue Bai,&nbsp;Anteng Shi,&nbsp;Yu Nie,&nbsp;Shengshou Hu,&nbsp;Hong Lian","doi":"10.1111/jcmm.70493","DOIUrl":"https://doi.org/10.1111/jcmm.70493","url":null,"abstract":"<p>Loss-of-function variants in the <i>FLNC</i> gene, which encodes Filamin C, cause dilated cardiomyopathy with a high risk of life-threatening arrhythmias. Therapies targeting the underlying mechanism of <i>FLNC</i>-related dilated cardiomyopathy remain limited. In this study, we observed that deletion of <i>Flnc</i> in cardiomyocytes of mice led to prominent ventricular dilation, cardiac dysfunction, and cardiac fibrosis. This phenotype closely resembles <i>FLNC</i>-related dilated cardiomyopathy in humans. RNA sequencing analysis revealed activation of protein disulfide isomerase (PDI) in <i>Flnc</i>-deleted cardiac tissues, as confirmed by immunoblotting. Treatment with the specific PDI inhibitor E64FC26 improved cardiac function, reduced cardiac fibrosis, and decreased cardiomyocyte apoptosis in cardiomyocyte-specific <i>Flnc</i>-deleted mice. We provide evidence that PDI is involved in the cardiac remodeling induced by Filamin C deficiency, and that treatment with the PDI inhibitor resulted in beneficial effects in mice with dilated cardiomyopathy caused by <i>Flnc</i> deletion. Our findings suggest that PDI could be a promising therapeutic target for <i>FLNC</i>-related dilated cardiomyopathy.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70493","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Notch1 and Major Vault Proteins Modulate Temozolomide Resistance in Glioblastoma","authors":"Cengiz Tuncer,&nbsp;Ceyhan Hacioglu","doi":"10.1111/jcmm.70474","DOIUrl":"https://doi.org/10.1111/jcmm.70474","url":null,"abstract":"<p>The development of resistance to chemotherapy in the case of aggressive glioblastoma multiforme (GBM) presents a significant treatment challenge. Dysregulation of the Notch signalling pathway promotes tumour proliferation in GBM cells. This study was that targeting the Notch signalling pathway could be a potential therapeutic approach for GBM. Initially, temozolomide-(TMZ)-resistant GBM cells were generated, and the effect of Notch1 on the expression of multiple resistance proteins within these cells was investigated. Subsequently, the expression of Notch-1 in GBM cells was reduced using siRNA. Results revealed a significant reduction in TMZ sensitivity in TMZ-resistant GBM cells, accompanied by a substantial increase in the expression of major vault protein-(MVP), O6-methylguanine-DNA-methyltransferase-(MGMT), and ATP-binding-cassette transporter-G2-(ABCG2). Furthermore, TMZ-resistant U87-R and U251-R cells exhibited higher proliferation rates compared to their parental control cells (U87 and U251). Additionally, we observed that downregulating Notch-1 signalling inhibited the proliferation of TMZ-resistant U87-R and U251-R cells. This downregulation led to the inactivation of MGMT, ABCG2, and MVP. Importantly, it increased chemosensitivity to TMZ, particularly by downregulating MVP expression. Consequently, Notch1 could serve as a potential therapeutic target for GBM cells and may be effective in preventing TMZ resistance by targeting MVP, as well as MGMT and ABCG2 in GBM cells.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70474","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intratumoral Heterogeneity and Immune Microenvironment in Hepatoblastoma Revealed by Single-Cell RNA Sequencing","authors":"Mingdi Ma,&nbsp;Chen Jin,&nbsp;Qian Dong","doi":"10.1111/jcmm.70482","DOIUrl":"https://doi.org/10.1111/jcmm.70482","url":null,"abstract":"<p>Hepatoblastoma (HB) is a common paediatric liver malignancy characterised by significant intratumoral heterogeneity and a complex tumour microenvironment (TME). Using single-cell RNA sequencing (scRNA-seq), we analysed 43,592 cells from three tumour regions and adjacent normal tissue of an HB patient. Our study revealed distinct cellular compositions and varying degrees of malignancy across different tumour regions, with the T1 region showing the highest malignancy and overexpression of HMGB2 and TOP2A. Survival analysis demonstrated that high HMGB2 expression is associated with poor prognosis and increased recurrence, suggesting its potential as a prognostic marker. Additionally, we identified a diverse immune microenvironment enriched with regulatory T cells (Tregs) and CD8⁺ effector memory T cells (Tem), indicating potential immune evasion mechanisms. Notably, CTLA-4 and PD-1 were highly expressed in Tregs and Tem cells, highlighting their potential as immunotherapy targets. Myeloid cells, including Kupffer cells and dendritic cells, also exhibited distinct functional roles in different tumour regions. This study provides the first comprehensive single-cell atlas of HB, revealing critical insights into its intratumoral heterogeneity and immune microenvironment. Our findings not only advance the understanding of HB biology but also offer new directions for precision medicine, including the development of targeted therapies and immunotherapeutic strategies to improve patient outcomes.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70482","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNA circHSPA8 Aggravates Metastasis by Acting as a Competitive Inhibitor of miR-195-5p to Upregulate WNT3A Expression in Breast Cancer","authors":"Zhuoying Han,&nbsp;Xiaojuan Yu,&nbsp;Chenlong Wang,&nbsp;Xiaoyu Song,&nbsp;Xiaomin Zhong,&nbsp;Renhua Guo,&nbsp;Weiyong Yu,&nbsp;Chao Luo","doi":"10.1111/jcmm.70499","DOIUrl":"https://doi.org/10.1111/jcmm.70499","url":null,"abstract":"<p>Circular RNA (circRNA) plays a vital role in the tumorigenicity and progression of cancer by regulating various biological behaviours. It acts as a microRNA sponge, disrupting transcription and the abnormal expression of oncogenes. Hsa_circ_0024715, a circRNA generated from cyclization at specific sites of the <i>HSPA8</i> gene, has been found to be highly expressed in breast cancer (BC) tissue based on non-coding RNA high-throughput sequencing. However, its functions remain poorly understood. In this study, we performed qPCR to evaluate the expression of circHSPA8 in BC tissues. Survival analysis in a prospective cohort revealed that high expression of circHSPA8 is associated with poor prognosis and lymphoid node metastasis. Overexpression of circHSPA8 in MCF-7 cells significantly enhanced their proliferative and invasive abilities, whereas knockdown of circHSPA8 in MDA-MB-231 cells significantly reduced their proliferative and invasive abilities. We found that circHSPA8 can promote epithelial–mesenchymal transition (EMT) in BC cells, primarily by upregulating the expression of <i>WNT3A</i>. This process depends on the sponging and inhibition of miR-195-5p, which suppresses the proliferation, invasion, and metastasis of BC cells. In vivo experiments further confirmed that circHSPA8 can promote the intravasation and extravasation of BC cells as well as the formation of metastatic lesions in the lungs. In summary, these data demonstrate that circHSPA8 promotes EMT by acting as a competitive inhibitor of miR-195-5p to upregulate the expression of <i>WNT3A</i> in BC, suggesting that dysregulation of circRNA in BC might be a pathological factor and potential therapeutic target.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70499","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}