Molecular and Cellular Biochemistry最新文献

{"title":"Cardiovascular protective effects of natural flavonoids on intestinal barrier injury.","authors":"Peng Zhou, Hui-Juan Xu, Liang Wang","doi":"10.1007/s11010-025-05213-2","DOIUrl":"10.1007/s11010-025-05213-2","url":null,"abstract":"<p><p>Natural flavonoids may be utilized as an important therapy for cardiovascular diseases (CVDs) caused by intestinal barrier damage. More research is being conducted on the protective properties of natural flavonoids against intestinal barrier injury, although the underlying processes remain unknown. Thus, the purpose of this article is to present current research on natural flavonoids to reduce the incidence of CVDs by protecting intestinal barrier injury, with a particular emphasis on intestinal epithelial barrier integrity (inhibiting oxidative stress, regulating inflammatory cytokine expression, and increasing tight junction protein expression). Furthermore, the mechanisms driving intestinal barrier injury development are briefly explored, as well as natural flavonoids having CVD-protective actions on the intestinal barrier. In addition, natural flavonoids with myocardial protective effects were docked with ZO-1 targets to find natural products with higher activity. These natural flavonoids can improve intestinal mechanical barrier function through anti-oxidant or anti-inflammatory mechanism, and then prevent the occurrence and development of CVDs.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3343-3362"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acid sphingomyelinase downregulation alleviates diabetic myocardial fibrosis in mice.","authors":"Changnong Chen, Yang Ji, Hao Liu, Lihua Pang, Jing Chen, Huanzhen Chen, Yujie Yao, Jinhao Ye, Sha Wang, Shiming Liu, Yun Zhong","doi":"10.1007/s11010-025-05206-1","DOIUrl":"10.1007/s11010-025-05206-1","url":null,"abstract":"<p><p>Increased activity of acid sphingomyelinase (ASMase) has been linked to diabetes and organ fibrosis. Nevertheless, the precise influence of ASMase on diabetic myocardial fibrosis and the corresponding molecular mechanisms remain elusive. In this study, we aim to elucidate whether ASMase contributes to diabetic myocardial fibrosis through the phosphorylation mediated by MAPK, thereby culminating in the development of diabetic cardiomyopathy (DCM). In vitro experiments utilized cardiac fibroblasts (CFs) isolated from wild-type mice (WT). For in vivo studies, ASMase knockout mice were generated through TALEN gene editing technology. Additionally, a diabetes mellitus model was established by intraperitoneal injection of Streptozotocin (STZ), involving both ASMase knockdown mice (ASMase^+/--STZ) and WT mice. CFs were subjected to incubation with amitriptyline (AMP) (2.5 μM), advanced glycation end products (AGEs), and small interfering RNA (siRNA) over a duration of 24 h. Experimental assessments encompassed EdU incorporation, transwell assays, and fluorescence staining, aimed at elucidating the functional characteristics of cardiac fibroblasts. The quantification of collagen I, phosphorylated MAPK levels within both cellular and murine cardiac contexts was accomplished through Western blot analysis. In the ASMase^±-STZ group, mice exhibited attenuated myocardial fibrosis and ameliorated cardiac diastolic function in comparison to the WT-STZ group. Furthermore, treatment of CFs with AMP and siRNA demonstrated a suppressive effect on the proliferation and fibrotic expression induced by AGEs in CFs. Our investigation unveiled that ASMase modulates myocardial fibrosis through the TGF-β-Smad3 and MAPK pathways, elucidating the intricate molecular mechanisms underlying the observed effects. Our findings indicate that ASMase plays a vital role in myocardial fibrosis in DCM, providing a foundation for developing new therapeutic strategies for the prevention and control of DCM.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3749-3763"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MTMR7 attenuates the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary hypertension by suppressing ERK/STAT3 signaling.","authors":"Jia Wang, Bing Xuan, Baomei Song, Ting Wang, Cong Lan, Wei Guo, Yongjian Yang, Xiongshan Sun","doi":"10.1007/s11010-025-05217-y","DOIUrl":"10.1007/s11010-025-05217-y","url":null,"abstract":"<p><p>Myotubularin-related protein 7 (MTMR7) represses proliferation in several cell types. However, the role of MTMR7 in pulmonary arterial smooth muscle cells (PASMCs) and pulmonary hypertension (PH) is unknown. The present study aimed to explore the role of MTMR7 in PH, as well as in the proliferation and migration of PASMCs. A monocrotaline (MCT)-induced PH mouse model was established. Mtmr7-transgenic (Mtmr7-Tg) mice and an adenovirus carrying the Mtmr7 vector (Ad-Mtmr7) were used to achieve MTMR7 overexpression in vivo and in vitro, respectively. Ultrasound and morphological analyses were used to evaluate the severity of PH. Cell counting kit-8 (CCK-8) and Ki-67 immunofluorescence staining were used to assess the proliferation of PASMCs. Wound-healing and transwell assays were used to assess cell migration. MTMR7 was upregulated in hypoxia-stimulated PASMCs and pulmonary arteries of MCT-treated mice. When compared with wild-type mice, PH-associated symptoms were significantly ameliorated in Mtmr7-Tg mice after MCT treatment when compared to wild-type mice. MTMR7 overexpression suppressed the proliferation and migration of PASMCs induced by hypoxia. Further experiments revealed that MTMR7 inhibited the phosphorylation levels of ERK1/2 and STAT3 both in vivo and in vitro. Restoring either ERK1/2 or STAT3 eliminated the protective role of MTMR7 against PH. Additionally, restoring ERK1/2 also reversed MTMR7-mediated STAT3 dephosphorylation. Our study highlights the inhibitory role of MTMR7 in PH and in the proliferation and migration of PASMCs and thus provides a novel potent therapeutic strategy for treating PH.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3799-3812"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exogenous hydrogen sulfide improves non-alcoholic fatty liver disease by inhibiting endoplasmic reticulum stress/NLRP3 inflammasome pathway.","authors":"Xiaodi Fu, Qi Zhang, Yuhang Chen, Ying Li, Honggang Wang","doi":"10.1007/s11010-025-05220-3","DOIUrl":"10.1007/s11010-025-05220-3","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide, and its exact pathogenesis has not been fully studied. Hydrogen sulfide (H₂S) is the third gas signaling molecule discovered in mammals, following nitric oxide and carbon monoxide. It has the effects of anti-inflammation, anti-apoptosis, and so on, thereby playing an important role in many diseases. However, the role and mechanism of exogenous H₂S in NAFLD are not fully understood. In this study, we constructed in vitro and in vivo NAFLD models by feeding mice a high-fat diet and stimulating hepatocytes with palmitic acid, respectively, to investigate the improvement effect and mechanism of exogenous H₂S on NAFLD. The results showed that NaHS (a donor of H₂S) treatment alleviated lipid accumulation, inflammation, apoptosis and pyroptosis, and downregulated endoplasmic reticulum (ER) stress and nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NRRP3) inflammasome in NAFLD. The activation of NLRP3 inflammasome weakened NaHS improvement of NAFLD, indicating that exogenous H₂S ameliorated NAFLD by inhibiting NLRP3 inflammasome-mediated lipid synthesis, inflammation, apoptosis and pyroptosis. Similarly, the activation of ER stress weakened NaHS improvement of NAFLD and NaHS inhibition of NLRP3 inflammasome, indicating that exogenous H₂S suppressed NLRP3 inflammasome by downregulating ER stress, thus improving NAFLD. Additionally, the protein expressions of NLRP3 and cleaved caspase-1 were downregulated after inhibiting the reactive oxygen species (ROS)/extracellular signal-regulated kinases (ERK) and ROS/thioredoxin-interacting protein (TXNIP) pathways, indicating that ER stress activated NLRP3 inflammasome through the ROS/ERK and ROS/TXNIP pathways. In conclusion, our results indicated that exogenous H₂S inhibited NLRP3 inflammasome-mediated hepatocytes inflammation, lipid synthesis, apoptosis and pyroptosis by downregulating ER stress, thereby improving NAFLD; Furthermore, ER stress activated NLRP3 inflammasome through the ROS/ERK and ROS/TXNIP pathways in NAFLD. ER stress/NLRP3 inflammasome is expected to become a new target of H₂S for treating NAFLD.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3813-3839"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synaptic-mitochondrial transport: mechanisms in neural adaptation and degeneration.","authors":"Yang Ding, Huan Yang, Jie Gao, Can Tang, Yu-Yuan Peng, Xin-Mei Ma, Sen Li, Hai-Yan Wang, Xiu-Min Lu, Yong-Tang Wang","doi":"10.1007/s11010-025-05209-y","DOIUrl":"10.1007/s11010-025-05209-y","url":null,"abstract":"<p><p>Synaptic plasticity is the basis for the proper functioning of the central nervous system. Synapses are the contact points between neurons and are crucial for information transmission, the structure and function of synapses change adaptively based on the different activities of neurons, thus affecting processes such as learning, memory, and neural development and repair. Synaptic activity requires a large amount of energy provided by mitochondria. Mitochondrial transport proteins regulate the positioning and movement of mitochondria to maintain normal energy metabolism. Recent studies have shown a close relationship between mitochondrial transport proteins and synaptic plasticity, providing a new direction for the study of adaptive changes in the central nervous system and new targets for the treatment of neurodegenerative diseases.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3399-3411"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of combination of zofenopril and different diuretics on regression of myocardial reperfusion injury and oxidative status in spontaneously hypertensive rats.","authors":"Maja Savic, Nevena Dragasevic, Jasmina Sretenovic, Katarina Mihajlovic, Marijana Andjic, Katarina Djordjevic, Bozidar Pindovic, Vladimir Zivkovic, Ivan Srejovic, Sergey Bolevich, Stefani Bolevich, Vladimir Jakovljevic, Tamara Nikolic Turnic","doi":"10.1007/s11010-024-05203-w","DOIUrl":"10.1007/s11010-024-05203-w","url":null,"abstract":"<p><p>As several decades of research have shown the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitors alone or in combination with diuretics, we were interested in investigating the effects of subchronic therapy of these drugs on ischemia-reperfusion (I/R) damage to the heart, as well as their influence on oxidative status. The research was conducted on 40 spontaneously hypertensive male Wistar Kyoto rats, divided into 4 groups. Animals were treated for four weeks with 10 mg/kg/day zofenopril alone or in combination with hydrochlorothiazide, indapamide and spironolactone per os. After the treatment, hemodynamic measurements, echocardiography and assessment of myocardial function were performed according to Langendorff's retrograde perfusion method. The induced global ischemia model involved 20 min of ischemia followed by 30 min of reperfusion to the heart (I20:R30). Markers of oxidative stress were determined spectrophotometrically from plasma and erythrocyte lysates. Heart and kidney tissue samples were pathohistologically analyzed. Treatment with a combination of ACE inhibitors and diuretics significantly lowered blood pressure in spontaneously hypertensive rats, alleviated left ventricular hypertrophy and increased ejection fraction. On the other hand, treatment with zofenopril and diuretics showed pro-oxidative potential. Pathohistological analysis of heart and kidney tissue samples indicates that subchronic administration of antihypertensive agents does not lead to significant changes in these organs. Since the antihypertensive therapy was relatively short (only 4 weeks), in order to elucidate or deny the prooxidative mechanism, additional studies of a longer time interval are needed and planned.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3695-3708"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor microenvironment noise-induced polarization: the main challenge in macrophages' immunotherapy for cancer.","authors":"Jesus Sierra, Ugo Avila-Ponce de León, Pablo Padilla-Longoria","doi":"10.1007/s11010-025-05205-2","DOIUrl":"10.1007/s11010-025-05205-2","url":null,"abstract":"<p><p>Disturbance of epigenetic processes can lead to altered gene function and malignant cellular transformation. In particular, changes in the epigenetic landscape are a central topic in cancer biology. The initiation and progression of cancer are now recognized to involve both epigenetic and genetic alterations. In this paper, we study the epigenetic mechanism (related to the tumor microenvironment) responsible for increasing tumor-associated macrophages that promote the occurrence and metastasis of tumor cells, support tumor angiogenesis, inhibit T-cell-mediated anti-tumor immune response, and lead to tumor progression. We show that the tumor benefits from the macrophages' high degree of plasticity and larger epigenetic basins corresponding to phenotypes that favor cancer development through a process that we call noise-induced polarization. Moreover, we propose a mechanism to promote the appropriate epigenetic stability for immunotherapies involving macrophages, which includes p53 and APR-246 (eprenetapopt). Our results show that a combination therapy may be necessary to ensure the proper epigenetic stability of macrophages, which otherwise will contribute to cancer progression. On the other hand, we conclude that macrophages may remain in the anti-tumoral state in types of cancer that exhibit less TP53 mutation, like colorectal cancer; in these cases, macrophages' immunotherapy may be more suitable. We finally mention the relevance of the epigenetic potential (Waddington's landscape) as the backbone for our study, which encapsulates the biological information of the system.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3735-3747"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PAX2 induces endometrial cancer by inhibiting mitochondrial function via the CD133-AKT1 pathway.","authors":"Fu Hua, YunLang Cai","doi":"10.1007/s11010-025-05216-z","DOIUrl":"10.1007/s11010-025-05216-z","url":null,"abstract":"<p><p>Endometrial cancer (EC) is a malignancy of the endometrial epithelium. The prevalence and mortality rates associated with the disease are on the rise globally. A total of 20 cases of type I EC tissues were collected for transcriptomic sequencing, our findings indicate that PAX2 is highly expressed in EC tissues and is closely related to the pathogenesis of EC. PAX2 is a member of the paired homeobox domain family and has been linked to the development of a number of different tumours. In normal endometrial tissue, PAX2 is methylated; however, in EC, it is demethylated. Nevertheless, few studies have focused on its role in EC. A protein-protein interaction (PPI) analysis revealed a regulatory relationship between PAX2 and CD133, which in turn affects the activity of AKT1. CD133 is a well-known marker of tumor stem cells and is involved in tumor initiation, metastasis, recurrence, and drug resistance; AKT1 promotes cell survival by inhibiting apoptosis and is considered a major promoter of many types of cancer. Nevertheless, further investigation is required to ascertain whether PAX2 affects the progression of EC by regulating the CD133-AKT1 pathway. The present study demonstrated that PAX2 promoted cell proliferation, migration, invasion and adhesion, and inhibited apoptosis. Its mechanism of action was found to be the inhibition of mitochondrial oxidative phosphorylation, promotion of glycolysis, increase in mitochondrial copy number, and increase in the levels of reactive oxygen species (ROS) and hexokinase, as well as the concentration of mitochondrial calcium ions. This was achieved through the promotion of CD133 expression and the phosphorylation of AKT1. In conjunction with the aforementioned regulatory pathways, the progression of EC is facilitated.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3765-3781"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decorin: matrix-based pan-cancer tumor suppressor.","authors":"Sandeep Appunni, Anshul Saxena, Venkataraghavan Ramamoorthy, Yanjia Zhang, Mayur Doke, Sudheesh S Nair, Atulya Aman Khosla, Muni Rubens","doi":"10.1007/s11010-025-05224-z","DOIUrl":"10.1007/s11010-025-05224-z","url":null,"abstract":"<p><p>Studies have shown that decorin is a potent pan-cancer tumor suppressor that is under-expressed in most cancers. Decorin interacts with receptor tyrosine kinases and functions as a pan-receptor tyrosine kinase inhibitor, thereby suppressing oncogenic signals. Decorin deficiency promotes epithelial-to-mesenchymal transition and enhances cancer dissemination and metastasis. According to recent GLOBOCAN estimates, the most common cancers worldwide are breast, lung, prostate, colorectal, skin (non-melanoma), and stomach. Considering the burden of rising cancer incidence and the importance of discovering novel molecular markers and potential therapeutic agents for cancer management, we have outlined the possible expressional and clinicopathological significance of decorin in major cancers based on available pre-clinical and clinical studies. Measuring plasma decorin is a minimally invasive technique, and human studies have shown that it is useful in predicting clinical outcomes in cancer though it needs further validation. Oncolytic virus-mediated decorin gene transfer has shown significant anti-tumorigenic effects in pre-clinical studies, though its implication in human subjects is yet to be understood. Exogenous decorin delivery in experimental studies has been shown to mitigate cancer growth, but its therapeutic efficacy and safety are poorly understood. Future research is required to translate the tumor-suppressive action of decorin observed in preclinical experiments to therapeutic interventions in human subjects.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3569-3591"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulation of YY1 in M2 macrophages promotes secretion of exosomes containing hsa-circ-0000326 via super-enhancers to facilitate prostate cancer progression.","authors":"Han Guan, Huaixiang Tao, Jinguang Luo, Lilin Wan, Hao Hu, Long Chen, Zhiyuan Wen, Yuxuan Tao, Saisai Chen, Mingli Gu","doi":"10.1007/s11010-025-05222-1","DOIUrl":"10.1007/s11010-025-05222-1","url":null,"abstract":"<p><p>The transcription factor YY1 is significantly upregulated in M2 macrophages, which can facilitate the malignant progression of multiple cancers. However, the precise mechanisms underlying the influence of YY1-high M2 macrophages on prostate cancer (PCa) progression remain elusive. Therefore, this study aims to elucidate the specific mechanisms by which YY1-high M2 macrophages influence PCa progression. Cell proliferation was assessed through colony formation and CCK8 assays. To evaluate cell invasion and migration, Transwell and wound healing assays were utilized. We investigated the effects of exosomes derived from M2 macrophages overexpressing YY1 on PCa cells. Subsequently, circRNA microarrays and qRT-PCR identified a high level of hsa-circ-0000326 in exosomes. Nucleoplasmic isolation, luciferase reporter, RNA-pulldown assays elucidated the functions and downstream targets (miR-338-3p and AR) of hsa-circ-0000326. Chromatin immunoprecipitation sequencing, chromatin conformation capture, qRT-PCR, western blotting, and agarose-electrophoresis assays examined YY1's role in transcribing the hsa-circ-0000326 maternal gene MALAT1 as well as its modulation of QKI expression. Our results demonstrated that the secretion of exosomes enriched with hsa-circ-0000326 by YY1-overexpressing M2 macrophages contributes to PCa metastasis. Hsa-circ-0000326 functions as a competitive endogenous RNA against miR-338-3p to promote androgen receptor levels in PCa cells. Mechanistic investigations revealed that YY1 binds to the super-enhancer region of MALAT1 enhancing transcriptional activity for this gene. Simultaneously, YY1 upregulates QKI expression, facilitating splicing events leading to the formation of hsa-circ-0000326. Inhibiting exosomal hsa-circ-0000326 presents a potential therapeutic approach for treating metastatic PCa.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3873-3888"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}