Journal of Cellular Physiology最新文献

{"title":"Vacuolar H+-ATPase and Megalin-Mediated Prorenin Uptake: Focus on Elements Beyond the (Pro)Renin Receptor","authors":"Na Wang,&nbsp;Xifeng Lu,&nbsp;A. H. Jan Danser","doi":"10.1002/jcp.31518","DOIUrl":"10.1002/jcp.31518","url":null,"abstract":"<p>Megalin is a multiple-ligand receptor that contributes to protein reabsorption in the kidney. Recently, megalin was found to act as a novel endocytic receptor for prorenin. Internalization depended on the (pro)renin receptor. This receptor is an accessory protein of vacuolar H⁺-ATPase (V-ATPase), a complex consisting of 14 subunits and two accessory proteins. Here we explored whether V-ATPase elements other than the (P)RR affect megalin-mediated prorenin uptake. Using RNAi technology, we inhibited each individual V-ATPase subunit in megalin-expressing BN16 cells. Subsequently, we quantified megalin expression and the uptake of prorenin. To unravel the underlying molecular mechanisms, we investigated the adaptor proteins autosomal recessive hypercholesterolemia (ARH) and Disabled-2 (Dab2), which are important for the endocytosis of megalin, glycogen synthase kinase 3β (GSK3β), a regulatory factor of megalin recycling, and endoplasmic reticulum stress factors (ERSF). Silencing subunit <i>Atp6v</i>_<i>o</i><i>a1</i> reduced prorenin uptake by 19%, while silencing accessory protein <i>Atp6ap1</i> increased it by 15%. Silencing other subunits exerted a more modest or no effect. Silencing <i>Atp6v</i>_<i>o</i><i>a1</i> reduced surface megalin density, without altering its mRNA and protein levels, and this was associated with increased GSK3β phosphorylation and no change in ARH, Dab2, and ERSF. Silencing <i>Atp6ap1</i> increased megalin mRNA and protein expression and this was accompanied by upregulation of ARH and ERSF, while Dab2 expression was unaltered. In conclusion, V-ATPase units differently affect megalin-mediated reabsorption of prorenin, thereby offering novel pharmacological targets to not only affect renal renin-angiotensin system activity, but also to treat renal diseases that are associated with disturbed protein reabsorption, like Dent's disease.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914941","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":"miR-1224 Controls Mammal Cerebral Cortex Development by Targeting the 3’-UTR of the Dlx1 mRNA","authors":"Chenglong Liu,&nbsp;Liyu Zhou,&nbsp;Qingbai Liu,&nbsp;Li Ni,&nbsp;Jianping Yang","doi":"10.1002/jcp.31511","DOIUrl":"10.1002/jcp.31511","url":null,"abstract":"<div>\u0000 \u0000 <p>Neural precursor cells (NPCs) are a group of cells with self-renewal and multi-differentiation potential. MicroRNAs are required for neurogenesis in the central nervous system (CNS). Recent reports suggest that miR-1224 is important in human CNS diseases. However, its function in neurogenesis of brain development is unclear. The current study demonstrated the essential while developing the neocortex. The results showed that miR-1224 facilitated more NPCs to differentiate into neurons and oligodendrocytes while suppressing astrocyte differentiation. Conversely, inhibition of miR-1224 enhances the self-renewal ability and apoptosis of NPCs. The role of miR-1224 in the developing neocortex was examined by performing in-utero electroporation in vivo. It was observed that depletion impeded upper-layer Cux1⁺ neuronal generation while transforming radial glial cells into IPCs. However, miR-1224 promoted NPC proliferation in the ventricular zone. Moreover, miR-1224 negatively regulated the expression of <i>Dlx1</i> in NPCs by directly targeting the mRNA 3’-UTR region. These findings indicated that miR-1224 is a crucial NPC neurogenesis regulator during cortical development.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914939","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":"Primary Cilia Regulate the Homeostasis and Regeneration of the Stem Cell Niche in the Tooth","authors":"Xinming Zhang,&nbsp;Yuxin Cao,&nbsp;Mengge Wang,&nbsp;Yujia Li,&nbsp;Hanxiao Yin,&nbsp;Hua Ni,&nbsp;Song Yang,&nbsp;Fan Yu,&nbsp;Jia Yang,&nbsp;Lisu Peng,&nbsp;Meilin Hu,&nbsp;Dengwen Li,&nbsp;Dayong Liu","doi":"10.1002/jcp.31517","DOIUrl":"10.1002/jcp.31517","url":null,"abstract":"<div>\u0000 \u0000 <p>Primary cilia, functioning as crucial hubs for signal sensing and transduction, are integral to the development and maintenance of homeostasis across various organs. However, their roles in tooth homeostasis and repair remain inadequately understood. In this study, we reveal an indispensable role for primary cilia in regulating the homeostasis and regeneration of teeth, primarily through the regulation of cell proliferation. Using cilium-deficient mice, we demonstrate that disruption of ciliary homeostasis leads to abnormal tooth morphology, stunted growth and notably impaired tooth repair. RNA sequencing reveals a dysregulation in genes associated with various biological processes such as cell proliferation, differentiation, and cycle regulation. Furthermore, we show that cilium-deficient mice display reduced cell proliferation. Our findings highlight a critical function for primary cilia in the regulation of tooth homeostasis and regeneration and have important implications for the development of tooth regeneration therapies.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903230","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":"oar-miR-411a-5p Promotes Proliferation and Differentiation in Hu Sheep Myoblasts Under Heat Stress by Targeting SMAD2","authors":"Jiawei Lu,&nbsp;Yilan Liu,&nbsp;Huixia Li","doi":"10.1002/jcp.31515","DOIUrl":"10.1002/jcp.31515","url":null,"abstract":"<div>\u0000 \u0000 <p>MicroRNAs (miRNAs) are endogenous noncoding RNAs that produce a remarked effect on regulating posttranscriptional gene expression. Our previous study identified a decrease in the expression of oar-miR-411a-5p from umbilical plasma in intrauterine growth restriction (IUGR) Hu lambs subjected to maternal heat stress. In this study, we demonstrated that oar-miR-411a-5p could modulate skeletal muscle development. Overexpression of oar-miR-411a-5p significantly enhanced proliferation and differentiation in heat-stressed Hu sheep myoblasts while suppressing apoptosis. Conversely, inhibition of oar-miR-411a-5p resulted in opposing effects. Subsequently, RNAhybrid analysis revealed targeted sites between oar-miR-411a-5p and the 3′ untranslated region (UTR) of <i>SMAD2</i>. This suggested that <i>SMAD2</i> is a direct target gene of oar-miR-411a-5p, as its expression was negatively modulated by oar-miR-411a-5p, a finding corroborated by dual-luciferase assay and RT-qPCR. Furthermore, co-transfection of oar-miR-411a-5p and SMAD2 into Hu sheep myoblasts indicated that oar-miR-411a-5p modulated heat-stressed myoblast growth by targeting <i>SMAD2</i>. In conclusion, these findings elucidate the function of oar-miR-411a-5p in promoting the development of heat-stressed Hu sheep myoblasts, thereby enhancing our understanding of how miRNAs influence skeletal muscle growth in heat-stressed Hu sheep.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882145","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 Potential Role of Bone Morphogenetic Protein-2/-4 in Excessive Mechanical Overloading-Initiated Joint Degeneration","authors":"Rong-Ze Hsieh,&nbsp;Kuo-Chin Huang,&nbsp;Yu-Ping Su,&nbsp;Chung-Sheng Shi,&nbsp;Shun-Fu Chang","doi":"10.1002/jcp.31509","DOIUrl":"10.1002/jcp.31509","url":null,"abstract":"<div>\u0000 \u0000 <p>Excessive mechanical overloading of articular cartilage caused by excessive exercise or severe trauma is considered a critical trigger in the development of osteoarthritis (OA). However, the available clinical theranostic molecular targets and underlying mechanisms still require more elucidation. Here, we aimed to examine the possibility that bone morphogenetic proteins (BMPs) serve as molecular targets in rat cartilages and human chondrocytes under conditions of excessive mechanical overloading. Two rat models involving high-intensity running training and surgery for destabilization of medial meniscus, along with a cell model subjected to cyclic tensile strain, were established to simulate and investigate excessive mechanical overloading effects on cartilages/chondrocytes. We employed various methods, including immunohistochemistry, real-time polymerase chain reaction, western blot analysis, and enzyme-linked immunosorbent assay, to evaluate the expression, secretion, phosphorylation, and nuclear translocation of mRNA/proteins in cartilages and chondrocytes. Our findings revealed a simultaneous upregulation of BMP-2 and downregulation of BMP-4 in degenerated and inflamed cartilages and chondrocytes under excessive mechanical overloading. Furthermore, toll-like receptor 2 and nuclear factor kappa B-p50/p65 subunits signaling were identified as regulators governing this distinct expression pattern. Treatment with recombinant BMP-2 and/or BMP-4 proteins significantly ameliorated cartilage degeneration and chondrocyte inflammation induced by excessive mechanical overloading. These results strongly suggest that BMP-2 upregulation and BMP-4 downregulation might represent mechanisms for self-rescue and degeneration in damaged cartilage/chondrocytes, respectively. Our findings advance new insights that BMP-2/-4 might be potential molecular targets for excessive mechanical overloading-caused OA development and should be taken into account in future clinical applications.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877276","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":"Corrigendum: MiR-136-5p/FZD4 Axis Is Critical for Wnt Signaling-Mediated Myogenesis and Skeletal Muscle Regeneration","authors":"","doi":"10.1002/jcp.31508","DOIUrl":"10.1002/jcp.31508","url":null,"abstract":"<p><b>This article corrects the following:</b></p><p>miR-136-5p/FZD4 axis is critical for Wnt signaling-mediated myogenesis and skeletal muscle regeneration</p><p>Zhang, Donghao, Lingqian Yin, Zhongzhen Lin, Chunlin Yu, Jingjing Li, Peng Ren, Chaowu Yang, Mohan Qiu, and Yiping Liu</p><p>Journal of Cellular Physiology</p><p>https://doi.org/10.1002/jcp.31046</p><p>First published online: 23 May 2023</p><p><b>Correction text</b>:</p><p>A reviewer alerted the publisher that an earlier version of the revised manuscript had mistakenly been published in place of the accepted version of the article. This error occurred accidentally during the production process. We apologize for the error and any inconvenience that may have arisen as a result. The following changes align with the final accepted version of the article.</p><p>Figure 1F has been updated to include MyHC and Hoechst immunofluorescence staining of C2C12 at different stages. The corrected Figure 1 and associated legend are as follows:</p><p>The layout of Figure 4 has been changed to improve the visibility of the images of the cells in panels A and G. In addition, the MyoG Western blot image in panel E has been changed. The corrected Figure 4 and associated legend are as follows:</p><p>The Bcl+antagomir ZsGreen panel in Figure 5F has been replaced, and the title of the figure has been updated to accurately reflect that FZD4 expression attenuates antagomiR-136-5p-mediated muscle regeneration after injury. The corrected Figure 5 and associated legend are as follows:</p><p>Finally, the missing Supplemental Figure 1 has been added as follows:</p><p><b>Figure S1.</b> FZD4 promotes differentiation of C2C12 cells in vitro.</p><p>(A) Expression levels of PCNA, CDK2, MyoD and MyoG mRNA in C2C12 cells after overexpression of FZD4 (n = 9 cultures; mean ± SEM). (B) Western blot analysis analysis of the PCNA and MyoG protein levels in C2C12 cells. β-Tubulin was used as an internal reference. (C) EdU and Hoechst (nuclei) staining analysis. The scale bar represents 100 μm. (D) Fold change of proliferation rate of C2C12 cells in each group (n = 6 cultures; mean ± SEM). EdU (red), Hoechst (blue). *<i>p</i> &lt; 0.05, **<i>p</i> &lt; 0.01, ***<i>p</i> &lt; 0.001.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.31508","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877275","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":"Tissue Engineering 3D-Printed Scaffold Using Allograft/Alginate/Gelatin Hydrogels Coated With Platelet-Rich Fibrin or Adipose Stromal Vascular Fraction Induces Osteogenesis In Vitro","authors":"Sahar Baniameri,&nbsp;Hossein Aminianfar,&nbsp;Niusha Gharehdaghi,&nbsp;Amir-Ali Yousefi-Koma,&nbsp;Sadra Mohaghegh,&nbsp;Hanieh Nokhbatolfoghahaei,&nbsp;Arash Khojasteh","doi":"10.1002/jcp.31497","DOIUrl":"10.1002/jcp.31497","url":null,"abstract":"<div>\u0000 \u0000 <p>Incorporating autologous patient-derived products has become imperative to enhance the continually improving outcomes in bone tissue engineering. With this objective in mind, this study aimed to evaluate the osteogenic potential of 3D-printed allograft-alginate-gelatin scaffolds coated with stromal vascular fraction (SVF) and platelet-rich fibrin (PRF). The primary goal was to develop a tissue-engineered construct capable of facilitating efficient bone regeneration through the utilization of biomaterials with advantageous properties and patient-derived products. To achieve this goal, 3D-printed gelatin, allograft, and alginate scaffolds were utilized, along with stem cells derived from the buccal fat pad and human-derived components (PRF, SVF). Cells were seeded onto scaffolds, both with and without SVF/PRF, and subjected to comprehensive assessments including adhesion, proliferation, differentiation (gene expression and protein secretion levels), penetration, and gene expression analysis over 14 days. The data was reported as mean ± standard deviation (SD). Two-way or one-way analysis of variance (ANOVA) was performed, followed by a Tukey post hoc test for multiple comparisons. Statistical significance was determined as a <i>p</i> value below 0.05. The scaffolds demonstrated structural integrity, and the addition of PRF coatings significantly enhanced cellular adhesion, proliferation, and differentiation compared to other groups. Gene expression analysis showed increased expression of osteogenic and angiogenic markers in the PRF-coated scaffolds. These findings highlight the promising role of PRF-coated scaffolds in promoting osteogenesis and facilitating bone tissue regeneration. This study emphasizes the development of patient-specific tissue-engineered constructs as a valuable approach for effective bone regeneration.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864225","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":"CBFβ Regulates RUNX3 ADP-Ribosylation to Mediate Homologous Recombination Repair","authors":"William E. Samsa,&nbsp;Zhen Zhang,&nbsp;Zihua Gong","doi":"10.1002/jcp.31503","DOIUrl":"10.1002/jcp.31503","url":null,"abstract":"<div>\u0000 \u0000 <p>RUNX3 is a master developmental transcriptional factor that has been implicated as a tumor suppressor in many cancers. However, the exact role of RUNX3 in cancer pathogenesis remains to be completely elucidated. Recently, it has emerged that RUNX3 is involved in the DNA damage response. Here, we demonstrate that heterodimerization of RUNX3 with CBFβ is necessary for its stability by protecting RUNX3 from RUNX3 ADP-ribosylation-dependent ubiquitination and degradation. We further identify new amino acid residues that are targets for PARylation and demonstrate that RUNX3 PARylation at these residues is necessary for localization of RUNX3 to DNA double strand break sites (DBSs). We also demonstrate that both RUNX3 PARylation and CBFβ heterodimerization with RUNX3 positively regulates homologous recombination (HR) repair, in part by promoting the recruitment of CtIP and phospho-RPA2 to the DBSs to mediate HR repair. In summary, we provide evidence that RUNX3 regulates HR repair activity in a PARylation-dependent manner.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854241","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":"Novel Therapeutic Strategies Targeting Fibroblasts to Improve Heart Disease","authors":"Yujuan Li","doi":"10.1002/jcp.31504","DOIUrl":"10.1002/jcp.31504","url":null,"abstract":"<div>\u0000 \u0000 <p>Cardiac fibrosis represents the terminal pathological manifestation of various heart diseases, with the formation of fibroblasts playing a pivotal role in this process. Consequently, targeting the formation and function of fibroblasts holds significant potential for improving outcomes in heart disease. Recent research reveals the considerable potential of fibroblasts in ameliorating cardiac conditions, demonstrating different functional characteristics at various time points and spatial locations. Therefore, precise modulation of fibroblast activity may offer an effective approach for treating cardiac fibrosis and achieving targeted therapeutic outcomes. In this review, we focus on the fate and inhibition of fibroblasts, analyze their dynamic changes in cardiac diseases, and propose a framework for identifying markers of fibroblast activation mechanisms and selecting optimal time windows for therapeutic intervention. By synthesizing research findings in these areas, we aim to provide new strategies and directions for the precise treatment of fibroblasts in cardiac diseases.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846675","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":"RRM2 Is a Putative Biomarker and Promotes Bladder Cancer Progression via PI3K/AKT/mTOR Pathway","authors":"Linfa Guo,&nbsp;Yiqiao Zhao,&nbsp;Xiaojie Bai,&nbsp;Xiaolong Wang,&nbsp;Kuerban Tuoheti,&nbsp;Yuanfei Cao,&nbsp;Yingtong Zuo,&nbsp;Xinhua Zhang,&nbsp;Tongzu Liu","doi":"10.1002/jcp.31501","DOIUrl":"10.1002/jcp.31501","url":null,"abstract":"<div>\u0000 \u0000 <p>Bladder cancer (BLCA) is the tenth most common cancer worldwide, characterized by its high recurrence and progression rates. Thus, identifying prognostic biomarkers and understanding its underlying mechanisms are imperative to enhance patient outcomes. In this study, we aimed to investigate the prognostic significance, expression, functional activity, and underlying mechanisms of RRM2 in BLCA. RRM2 expression and its association with pathological grading and survival were investigated in samples from TCGA dataset and BLCA tissue microarray. CCK8 assays, colony formation assays, wound healing, and transwell assays were performed to assess the role of RRM2 in BLCA cell proliferation and migration. Western blot was employed to investigate alterations in markers associated with epithelial-to-mesenchymal transition (EMT), apoptosis, and cell cycle regulation. Gene set enrichment analysis was performed to investigate the biological processes associated with RRM2, which were subsequently validated. The expression of RRM2 was significantly elevated in both BLCA tissues and cells. Our results also indicated a positive correlation between RRM2 expression and high tumor stage, high tumor grade, and poor survival. Knockdown of RRM2 inhibited cell proliferation and migration of BLCA. RRM2 knockdown significantly induced apoptosis and arrested the cell cycle at the G0/G1 phase. Opposite results were observed in the RRM2 overexpression cells. Additionally, our study demonstrates that RRM2 promotes BLCA progression by activating the PI3K/AKT/mTOR pathway. RRM2 is remarkably correlated with poor prognosis in BLCA and facilitate its progression via PI3K/AKT/mTOR pathway. It is suggested that RRM2 might become an effective prognostic biomarker and potential therapeutic target for BLCA.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828602","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}