Biology Direct最新文献

{"title":"Pharmacological inhibition of mTORC1 reduces neural death and damage volume after MCAO by modulating microglial reactivity","authors":"Mario Villa-González, Marina Rubio, Gerardo Martín-López, Paula R. Mallavibarrena, Laura Vallés-Saiz, Denis Vivien, Francisco Wandosell, Maria José Pérez-Álvarez","doi":"10.1186/s13062-024-00470-5","DOIUrl":"https://doi.org/10.1186/s13062-024-00470-5","url":null,"abstract":"Ischemic stroke is a sudden and acute disease characterized by neuronal death, increment of reactive gliosis (reactive microglia and astrocytes), and a severe inflammatory process. Neuroinflammation is an early event after cerebral ischemia, with microglia playing a leading role. Reactive microglia involve functional and morphological changes that drive a wide variety of phenotypes. In this context, deciphering the molecular mechanisms underlying such reactive microglial is essential to devise strategies to protect neurons and maintain certain brain functions affected by early neuroinflammation after ischemia. Here, we studied the role of mammalian target of rapamycin (mTOR) activity in the microglial response using a murine model of cerebral ischemia in the acute phase. We also determined the therapeutic relevance of the pharmacological administration of rapamycin, a mTOR inhibitor, before and after ischemic injury. Our data show that rapamycin, administered before or after brain ischemia induction, reduced the volume of brain damage and neuronal loss by attenuating the microglial response. Therefore, our findings indicate that the pharmacological inhibition of mTORC1 in the acute phase of ischemia may provide an alternative strategy to reduce neuronal damage through attenuation of the associated neuroinflammation.","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"11 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140561511","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":"Circ_0002669 promotes osteosarcoma tumorigenesis through directly binding to MYCBP and sponging miR-889-3p","authors":"Ying Zhang, Yizhou Zhan, Zhaoyong Liu, Huancheng Guo, Dongchen Liu, Chuangzhen Chen","doi":"10.1186/s13062-024-00466-1","DOIUrl":"https://doi.org/10.1186/s13062-024-00466-1","url":null,"abstract":"Circular RNAs (circRNAs) are a class of highly multifunctional single-stranded RNAs that play crucial roles in cancer progression, including osteosarcoma (OS). Circ_0002669, generated from the dedicator of cytokinesis (DOCK) gene, was highly expressed in OS tissues, and negatively correlated with OS patient survival. Elevated circ_0002669 promoted OS cell growth and invasion in vivo and in vitro. By biotin pulldown and mass spectroscopy, we found that circ_0002669 directly bound to MYCBP, a positive regulator of c-myc, to prevent MYCBP from ubiquitin-mediated proteasome degradation. In addition, circ_0002669 interacted with miR-889-3p and served as a miRNA sponge to increase the expression of MYCBP, as determined by luciferase assays and RNA immunoprecipitation. Functional rescue experiments indicated MYCBP acted as a key factor for circ_0002669- and miR-889-3p-regulated OS cell proliferation and migration. Increased expression of c-myc-associated genes, such as CCND1, c-Jun and CDK4, were found in circ_0002669- and MYCBP-overexpressing OS cells. Our data thus provide evidence that circ_0002669 promotes OS malignancy by protecting MYCBP from protein ubiquitination and degradation and blocking miR-889-3p-mediated inhibition of MYCBP expression.","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"12 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140561499","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":"LINC00909 up-regulates pluripotency factors and promotes cancer stemness and metastasis in pancreatic ductal adenocarcinoma by targeting SMAD4","authors":"Zhenchong Li, Zuyi Ma, Shujie Wang, Qian Yan, Hongkai Zhuang, Zixuan Zhou, Chunsheng Liu, Yubin Chen, Mingqian Han, Zelong Wu, Shanzhou Huang, Qi Zhou, Baohua Hou, Chuanzhao Zhang","doi":"10.1186/s13062-024-00463-4","DOIUrl":"https://doi.org/10.1186/s13062-024-00463-4","url":null,"abstract":"Pancreatic cancer stem cells are crucial for tumorigenesis and cancer metastasis. Presently, long non-coding RNAs were found to be associated with Pancreatic Ductal Adenocarcinoma stemness characteristics but the underlying mechanism is largely known. Here, we aim to explore the function of LINC00909 in regulating pancreatic cancer stemness and cancer metastasis. The expression level and clinical characteristics of LINC00909 were verified in 80-paired normal pancreas and Pancreatic Ductal Adenocarcinoma tissues from Guangdong Provincial People’s Hospital cohort by in situ hybridization. RNA sequencing of PANC-1 cells with empty vector or vector encoding LINC00909 was experimented for subsequent bioinformatics analysis. The effect of LINC00909 in cancer stemness and metastasis was examined by in vitro and in vivo experiments. The interaction between LINC00909 with SMAD4 and the pluripotency factors were studied. LINC00909 was generally upregulated in pancreatic cancer tissues and was associated with inferior clinicopathologic features and outcome. Over-expression of LINC00909 enhanced the expression of pluripotency factors and cancer stem cells phenotype, while knock-down of LINC00909 decreased the expression of pluripotency factors and cancer stem cells phenotype. Moreover, LINC00909 inversely regulated SMAD4 expression, knock-down of SMAD4 rescued the effect of LINC00909-deletion inhibition on pluripotency factors and cancer stem cells phenotype. These indicated the effect of LINC00909 on pluripotency factors and CSC phenotype was dependent on SMAD4 and MAPK/JNK signaling pathway, another downstream pathway of SMAD4 was also activated by LINC00909. Specifically, LINC00909 was localized in the cytoplasm in pancreatic cancer cells and decreased the stability the SMAD4 mRNA. Finally, we found over-expression of LINC00909 not only accelerated tumor growth in subcutaneous mice models, but also facilitated tumorigenicity and spleen metastasis in orthotopic mice models. We demonstrate LINC00909 inhibits SMAD4 expression at the post-transcriptional level, which up-regulates the expression of pluripotency factors and activates the MAPK/JNK signaling pathway, leading to enrichment of cancer stem cells and cancer metastasis in pancreatic cancer.","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"29 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140170282","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":"Lactobacillus reuteri mitigates hepatic ischemia/reperfusion injury by modulating gut microbiota and metabolism through the Nrf2/HO-1 signaling","authors":"Leiyi Zhang, Xiaoxiang Gong, Juan Tan, Rongsen Zhang, Mingxia Li, Cong Liu, Chenhao Wu, Xiaojing Li","doi":"10.1186/s13062-024-00462-5","DOIUrl":"https://doi.org/10.1186/s13062-024-00462-5","url":null,"abstract":"This study seeks to investigate the impacts of Lactobacillus reuteri (L. reuteri) on hepatic ischemia-reperfusion (I/R) injury and uncover the mechanisms involved. Mice in the I/R groups were orally administered low and high doses of L.reuteri (L.reuteri-low and L. reuteri-hi; 1 × 1010 CFU/d and 1 × 1011 CFU/d), for 4 weeks prior to surgery. Following this, mice in the model group were treated with an Nrf2 inhibitor (ML-385), palmitoylcarnitine, or a combination of both. After treatment with L. reuteri, mice exhibited reduced levels of serum aminotransferase (ALT), aspartate aminotransferase (AST), and myeloperoxidase (MPO) activity, as well as a lower Suzuki score and apoptosis rate. L. reuteri effectively reversed the I/R-induced decrease in Bcl2 expression, and the significant increases in the levels of Bax, cleaved-Caspase3, p-p65/p65, p-IκB/IκB, p-p38/p38, p-JNK/JNK, and p-ERK/ERK. Furthermore, the administration of L. reuteri markedly reduced the inflammatory response and oxidative stress triggered by I/R. This treatment also facilitated the activation of the Nrf2/HO-1 pathway. L. reuteri effectively counteracted the decrease in levels of beneficial gut microbiota species (such as Blautia, Lachnospiraceae NK4A136, and Muribaculum) and metabolites (including palmitoylcarnitine) induced by I/R. Likewise, the introduction of exogenous palmitoylcarnitine demonstrated a beneficial impact in mitigating hepatic injury induced by I/R. However, when ML-385 was administered prior to palmitoylcarnitine treatment, the previously observed effects were reversed. L. reuteri exerts protective effects against I/R-induced hepatic injury, and its mechanism may be related to the promotion of probiotic enrichment, differential metabolite homeostasis, and the Nrf2/HO-1 pathway, laying the foundation for future clinical applications.","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140150973","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":"Exploring the role of GhN/AINV23: implications for plant growth, development, and drought tolerance","authors":"Kaikai Qiao, Qingtao Zeng, Jiaoyan Lv, Lingling Chen, Juxin Hao, Ding Wang, Qifeng Ma, Shuli Fan","doi":"10.1186/s13062-024-00465-2","DOIUrl":"https://doi.org/10.1186/s13062-024-00465-2","url":null,"abstract":"Neutral/alkaline invertases (N/AINVs) play a crucial role in plant growth, development, and stress response, by irreversibly hydrolyzing sucrose into glucose and fructose. However, research on cotton in this area is limited. This study aims to investigate GhN/AINV23, a neutral/alkaline invertase in cotton, including its characteristics and biological functions. In our study, we analyzed the sequence information, three-dimensional (3D) model, phylogenetic tree, and cis-elements of GhN/AINV23. The localization of GhN/AINV23 was determined to be in the cytoplasm and cell membrane. Quantitative real-time polymerase chain reaction (qRT-PCR) results showed that GhN/AINV23 expression was induced by abscisic acid (ABA), exogenous sucrose and low exogenous glucose, and inhibited by high exogenous glucose. In Arabidopsis, overexpression of GhN/AINV23 promoted vegetative phase change, root development, and drought tolerance. Additionally, the virus-induced gene silencing (VIGS) assay indicated that the inhibition of GhN/AINV23 expression made cotton more susceptible to drought stress, suggesting that GhN/AINV23 positively regulates plant drought tolerance. Our research indicates that GhN/AINV23 plays a significant role in plant vegetative phase change, root development, and drought response. These findings provide a valuable foundation for utilizing GhN/AINV23 to improve cotton yield.","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"16 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140128412","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":"Mammalian enabled protein enhances tamoxifen sensitivity of the hormone receptor-positive breast cancer patients by suppressing the AKT signaling pathway.","authors":"Lifang He, Chuanghong She, Sen Jiang, Zhaochang Qi, Zihao Deng, Likeng Ji, Yukun Cui, Jundong Wu","doi":"10.1186/s13062-024-00464-3","DOIUrl":"10.1186/s13062-024-00464-3","url":null,"abstract":"<p><strong>Background: </strong>Mammalian enabled (MENA) protein is a member of the enabled/vasodilator stimulated phosphoprotein (Ena/VASP) protein family, which regulates cytoplasmic actin network assembly. It plays a significant role in breast cancer invasion, migration, and resistance against targeted therapy and chemotherapy. However, its role in the efficacy of endocrine therapy for the hormone receptor-positive (HR<sup>+</sup>) breast cancer patients is not known. This study investigated the role of MENA in the resistance against tamoxifen therapy in patients with HR<sup>+</sup> breast cancer and the underlying mechanisms.</p><p><strong>Methods: </strong>MENA expression levels in the clinical HR<sup>+</sup> breast cancer samples (n = 119) were estimated using immunohistochemistry (IHC) to determine its association with the clinicopathological features, tamoxifen resistance, and survival outcomes. Western blotting (WB) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis was performed to estimate the MENA protein and mRNA levels in the tamoxifen-sensitive and -resistant HR<sup>+</sup> breast cancer cell lines. Furthermore, CCK8, colony formation, and the transwell invasion and migration assays were used to analyze the effects of MENA knockdown on the biological behavior and tamoxifen sensitivity of the HR<sup>+</sup> breast cancer cell lines. Xenograft tumor experiments were performed in the nude mice to determine the tumor growth rates and tamoxifen sensitivity of the control and MENA knockdown HR<sup>+</sup> breast cancer cells in the presence and absence of tamoxifen treatment. Furthermore, we estimated the growth rates of organoids derived from the HR<sup>+</sup> breast cancer patients (n = 10) with high and low MENA expression levels when treated with tamoxifen.</p><p><strong>Results: </strong>HR<sup>+</sup> breast cancer patients with low MENA expression demonstrated tamoxifen resistance and poorer prognosis compared to those with high MENA expression. Univariate and multivariate Cox regression analysis demonstrated that MENA expression was an independent predictor of tamoxifen resistance in patients with HR<sup>+</sup> breast cancer. MENA knockdown HR<sup>+</sup> breast cancer cells showed significantly reduced tamoxifen sensitivity in the in vitro experiments and the in vivo xenograft tumor mouse model compared with the corresponding controls. Furthermore, MENA knockdown increased the in vitro invasion and migration of the HR<sup>+</sup> breast cancer cells. HR<sup>+</sup> breast cancer organoids with low MENA expression demonstrated reduced tamoxifen sensitivity than those with higher MENA expression. Mechanistically, P-AKT levels were significantly upregulated in the MENA-knockdown HR + breast cancer cells treated with or without 4-OHT compared with the corresponding controls.</p><p><strong>Conclusions: </strong>This study demonstrated that downregulation of MENA promoted tamoxifen resistance in the ","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"21"},"PeriodicalIF":5.5,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10921784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140064894","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":"Dysregulation and antimetastatic function of circLRIG1 modulated by miR-214-3p/LRIG1 axis in bladder carcinoma","authors":"Shiliang Cheng, Chunguang Li, Lu Liu, Xinli Liu, Meng Li, Jinhua Zhuo, Jue Wang, Wen Zheng, Zhongmin Wang","doi":"10.1186/s13062-023-00446-x","DOIUrl":"https://doi.org/10.1186/s13062-023-00446-x","url":null,"abstract":"CircLRIG1, a newly discovered circRNA, has yet to have its potential function and biological processes reported. This study explored the role of circLRIG1 in the development and progression of bladder carcinoma and its potential molecular mechanisms. Techniques such as qRT-PCR, Western blot, various cellular assays, and in vivo models were used to investigate mRNA and protein levels, cell behavior, molecular interactions, and tumor growth. The results showed that both circLRIG1 and LRIG1 were significantly reduced in bladder carcinoma tissues and cell lines. Low circLRIG1 expression was associated with poor patient prognosis. Overexpressing circLRIG1 inhibited bladder carcinoma cell growth, migration, and invasion, promoted apoptosis, and decreased tumor growth and metastasis in vivo. Importantly, circLRIG1 was found to sponge miR-214-3p, enhancing LRIG1 expression, and its overexpression also modulated protein levels of E-cadherin, N-cadherin, Vimentin, and LRIG1. Similar effects were observed with LRIG1 overexpression. Notably, a positive correlation was found between circLRIG1 and LRIG1 expression in bladder carcinoma tissues. Additionally, the tumor-suppressing effect of circLRIG1 was reversed by overexpressing miR-214-3p or silencing LRIG1. The study concludes that circLRIG1 suppresses bladder carcinoma progression by enhancing LRIG1 expression via sponging miR-214-3p, providing a potential strategy for early diagnosis and treatment of bladder carcinoma.","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"66 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140056608","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":"PHF5A promotes esophageal squamous cell carcinoma progression via stabilizing VEGFA","authors":"Zhiwei Chang, Yongxu Jia, Ming Gao, Lijie Song, Weijie Zhang, Ruihua Zhao, Dandan Yu, Xiaolei Liu, Jing Li, Yanru Qin","doi":"10.1186/s13062-023-00440-3","DOIUrl":"https://doi.org/10.1186/s13062-023-00440-3","url":null,"abstract":"Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Current therapeutic effect is far from satisfaction. Hence, identifying susceptible genes and potential targets is necessary for therapy of ESCC patients. Plant homeodomain (PHD)-finger domain protein 5 A (PHF5A) expression in ESCC tissues was examined by immunohistochemistry. RNA interference was used for in vitro loss-of-function experiments. In vivo assay was performed using xenograft mice model by subcutaneous injection. Besides, microarray assay and co-immunoprecipitation experiments were used to study the potential downstream molecules of PHF5A in ESCC. The molecular mechanism between PHF5A and vascular endothelial growth factor A (VEGFA) was explored by a series of ubiquitination related assays. We found that PHF5A was highly expressed in ESCC tissues compared to normal tissues and that was correlated with poor prognosis of ESCC. Loss-of-function experiments revealed that PHF5A silence remarkably inhibited cell proliferation, migration, and induced apoptosis as well as cell cycle arrest. Consistently, in vivo assay demonstrated that PHF5A deficiency was able to attenuate tumor growth. Furthermore, molecular studies showed that PHF5A silencing promoted VEGFA ubiquitination by interacting with MDM2, thereby regulating VEGFA protein expression. Subsequently, in rescue experiments, our data suggested that ESCC cell viability and migration promoted by PHF5A were dependent on intact VEGFA. Finally, PI3K/AKT signaling rescue was able to alleviate shPHF5A-mediated cell apoptosis and cell cycle arrest. PHF5A is a tumor promoter in ESCC, which is dependent on VEGFA and PI3K/AKT signaling. PHF5A might serve as a potential therapeutic target for ESCC treatment.","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140005211","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":"Unlocking hepatocellular carcinoma aggression: STAMBPL1-mediated TRAF2 deubiquitination activates WNT/PI3K/NF-kb signaling pathway.","authors":"Zhihuai Wang, Yinjie Zhang, Yuhang Shen, Haiyang Zhou, Yuan Gao, Chunfu Zhu, Xihu Qin","doi":"10.1186/s13062-024-00460-7","DOIUrl":"10.1186/s13062-024-00460-7","url":null,"abstract":"<p><p>STAM Binding Protein Like 1 (STAMBPL1), functions as a deubiquitinase (DUB) and plays a significant role in various types of cancers. However, its effect as a DUB participating in the HCC tumorigenesis and progression still unknown. In the study, the upregulation and strong prognosis value of STAMBPL1 were identified in HCC patients. Functionally, STAMBPL1 significantly promoted HCC cells proliferation and metastasis, and it interacts with TRAF2 and stabilize it via the deubiquitination at the K63 residue. The TRAF2 upregulation stabilized by STAMBPL1 overexpression transfers of P65 protein into the nucleus and activates the WNT/PI3K/ NF-kb signaling pathway. The 251-436 sites of STAMBPL1 particularly interact with the 294-496 sites of TRAF2, thereby exerting the function of DUB and removing the ubiquitin molecules attached to TRAF2. Our research unveiled a new function of STAMBPL1 in mediating TRAF2 deubiquitination and stabilization, thereby activating the WNT/PI3K/NF-kb signaling pathway, suggesting its potential as a novel biomarker and therapeutic target for HCC.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"18"},"PeriodicalIF":5.7,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989307","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":"Comprehensive analysis of mitochondria-related genes indicates that PPP2R2B is a novel biomarker and promotes the progression of bladder cancer via Wnt signaling pathway","authors":"Du Shen, Shaosan Kang","doi":"10.1186/s13062-024-00461-6","DOIUrl":"https://doi.org/10.1186/s13062-024-00461-6","url":null,"abstract":"Bladder cancer (BC) is the fourth and tenth most common malignancy in men and women worldwide, respectively. The complexity of the molecular biological mechanism behind BC is a major contributor to the lack of effective treatment management of the disease. The development and genesis of BC are influenced by mitochondrial retrograde control and mitochondria-nuclear cross-talk. However, the role of mitochondrial-related genes in BC remains unclear. In this study, we analyzed TCGA datasets and identified 752 DE-MRGs in BC samples, including 313 down-regulated MRGs and 439 up-regulated MRGs. Then, the results of machine-learning screened four critical diagnostic genes, including GLRX2, NMT1, PPP2R2B and TRAF3IP3. Moreover, we analyzed their prognostic value and confirmed that only PPP2R2B was associated with clinical prognosis of BC patients and Cox regression assays validated that PPP2R2B expression was a distinct predictor of overall survival in BC patients. Them, we performed RT-PCR and found that PPP2R2B expression was distinctly decreased in BC specimens and cell lines. Functional experiments revealed that overexpression of PPP2R2B distinctly suppressed the proliferation, migration and invasion of BC cells via Wnt signaling pathway. In summary, these research findings offer potential molecular markers for the diagnosis and prognosis of BC, with the discovery of PPP2R2B particularly holding significant biological and clinical significance. This study provides valuable clues for future in-depth investigations into the molecular mechanisms of BC, as well as the development of new diagnostic markers and therapeutic targets.","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"22 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139967962","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}