Biochimica et biophysica acta. Molecular cell research最新文献

{"title":"RANKL regulates differentially breast cancer stem cell properties through its RANK and LGR4 receptors","authors":"Alejandro Ordaz-Ramos ,&nbsp;Jorge Diaz-Blancas ,&nbsp;Aketzalli Martínez-Cruz ,&nbsp;Rosario Castro-Oropeza ,&nbsp;Cecilia Zampedri ,&nbsp;Damaris P Romero-Rodríguez ,&nbsp;Mauricio Rodriguez-Dorantes ,&nbsp;Jorge Melendez-Zajgla ,&nbsp;Vilma Maldonado ,&nbsp;Karla Vazquez-Santillan","doi":"10.1016/j.bbamcr.2024.119888","DOIUrl":"10.1016/j.bbamcr.2024.119888","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer stem cells (BCSC) are a subpopulation responsible for cancer resistance and relapse. The receptor activator of nuclear factor kappa-Β ligand (RANKL) is a cytokine capable of activating RANK and LGR4 receptors. RANKL/RANK signaling maintains the self-renewal of BCSCs, however, the effect of RANKL via LGR4 remains unclear. Evidence from osteoclasts suggests that RANKL/LGR4 axis disrupts RANK signaling, leading to opposing cellular responses. Anti-RANKL inhibitors are potential agents for eradicating CSCs, but their effect on RANKL/LGR4 signal has not been demonstrated.</div></div><div><h3>Objective</h3><div>This project aimed to elucidate the role of RANKL in regulating stemness depending on the expression of its receptors.</div></div><div><h3>Methods</h3><div>We use in vitro and in vivo approaches to evaluate the effects of RANKL inhibition in stemness in low or high-LGR4 expressing cells. Furthermore, we analyze the effects of RANKL stimulation on the stemness of LGR4 or RANK overexpressing cells. Additionally, we evaluated the impact of RANKL/LGR4 signaling in the activity of Wnt/β-catenin and NF-κB signaling pathways.</div></div><div><h3>Results</h3><div>Our findings indicated that elevated RANKL expression is related to a favorable prognosis in patients with high LGR4 levels. Furthermore, RANKL inhibition decreased BCSC properties in LGR4-low cell lines, while it promoted migration in LGR4-high cells. Additionally, the RANKL/RANK axis activated NF-κB signaling and enhanced BCSCs in RANK-overexpressing cells. In contrast, in LGR4-overexpressing cells, RANKL failed to activate NF-κB but instead inhibited the Wnt/β-catenin pathway, leading to a reduction in BCSCs.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that RANKL exerts different responses according to the expression of its receptors.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 2","pages":"Article 119888"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812130","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":"GATA3: Orchestrating cellular fate through differentiation and proliferation","authors":"Rim Bacha ,&nbsp;Shona Pedersen ,&nbsp;Rana Ismail ,&nbsp;Nouran Alwisi ,&nbsp;Layla Al-Mansoori","doi":"10.1016/j.bbamcr.2024.119893","DOIUrl":"10.1016/j.bbamcr.2024.119893","url":null,"abstract":"<div><div>Cell proliferation and differentiation are two fundamental biological processes that occur in biological systems, tightly regulated by various factors such as transcription factors (TFs). Zinc finger proteins are TFs responsible for maintaining the biological balance via coordinating development and functionality within the living cells. GATA binding protein 3 (GATA3), one of the zinc finger proteins, plays an essential role in driving differentiation and proliferation-related processes, thereby contributing to the regulation of the dynamism and productivity of living cells. By elucidating the complex interactions governed by GATA3, this underscores its significance in maintaining cellular homeostasis. Thus, the current review delves into the molecular pathways influenced by GATA3, highlighting its involvement in multiple developmental processes of various tissues and body sites, particularly in the hematopoietic system (T-cell differentiation), neural tissue differentiation, adipose tissue, as well as epithelial cell maturation.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 2","pages":"Article 119893"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891730","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":"Dedicator of cytokinesis protein 2 activates the epithelial–mesenchymal transition in renal fibrosis through the Rac1/PI3K/AKT pathway","authors":"Yuanyuan Jia ,&nbsp;Jing Sun ,&nbsp;Sha Chen ,&nbsp;Yu Bian ,&nbsp;Anni Jiang ,&nbsp;Haihai Liang ,&nbsp;Xuanyi Du","doi":"10.1016/j.bbamcr.2024.119894","DOIUrl":"10.1016/j.bbamcr.2024.119894","url":null,"abstract":"<div><div>Renal fibrosis is the most important feature of the progression of chronic kidney disease (CKD), and epithelial–mesenchymal transition (EMT) plays an important role in renal fibrosis. Dedicator of cytokinesis protein 2 (Dock2) is involved in the immune system and the development of a variety of fibrotic diseases. However, its specific role in renal fibrosis remains unclear. Therefore, in this study, we investigated the role and mechanism of Dock2 in renal fibrosis. We constructed an in vivo mouse model of unilateral ureteral obstruction (UUO) and an in vitro model of recombinant human transforming growth factor-β1 (TGF-β1)-induced HK-2 cells. The function and regulatory mechanism of Dock2 were studied via Western blotting, qRT-PCR, immunohistochemistry and immunofluorescence. First, Dock2 was more highly expressed in the kidneys of UUO mice than in those of sham-operated mice. A reduction in Dock2 can improve pathological changes in the kidney tissue of UUO mice, reduce the deposition of the extracellular matrix (ECM), and alleviate EMT. Silencing Dock2 reduced the activation of both the Rac1 pathway and the PI3K/AKT pathway. TGF-β1 promoted Dock2 expression in HK-2 cells in vitro. A decrease in Dock2 can inhibit the expression of Fibronectin, Collagen I, α-SMA and Vimentin and increase the level of E-cadherin. Treatment of HK-2 cells with the Rac1 activator 8-CPT or the PI3K/AKT pathway activator YS-49 inhibited the above changes induced by siDock2, indicating that Dock2 activates EMT in renal fibrosis through the Rac1/PI3K/AKT pathway. Our data suggest that Dock2 may be a potential target for renal fibrosis treatment.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 2","pages":"Article 119894"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891731","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":"Vasoactive intestinal peptide induces metabolic rewiring of human-derived cytotrophoblast cells to promote cell migration","authors":"Fátima Merech,&nbsp;Brenda Lara,&nbsp;Daiana Rios,&nbsp;Daniel Paparini,&nbsp;Rosanna Ramhorst,&nbsp;Vanesa Hauk,&nbsp;Claudia Pérez Leirós ,&nbsp;Daiana Vota","doi":"10.1016/j.bbamcr.2024.119886","DOIUrl":"10.1016/j.bbamcr.2024.119886","url":null,"abstract":"<div><div>The placenta has an extraordinary metabolic rate with high oxygen consumption. Extravillous cytotrophoblast cells (EVT) metabolism and function are critical to sustain their invasive phenotype supporting fetal development. Deficient EVT function underlies pregnancy complications as preeclampsia (PE) and fetal growth restriction (FGR). The vasoactive intestinal peptide (VIP) promotes human cytotrophoblast cell migration and invasion through mTOR signaling pathways suggesting its crucial role during placentation. Here we explored fatty acid uptake as well as lipid and glucose metabolism in human-derived cytotrophoblast cell function upon VIP stimulation. We found that VIP induced long chain fatty acid (LCFAs) uptake along with the expression of <em>FATP2</em> transporter, <em>CPT1</em> fatty acid oxidation (FAO)-rate limiting step importer, and lipid droplet accumulation. VIP induced the expression of glucose 6-P-dehydrogenase, a rate-limiting enzyme of the pentose phosphate pathway (PPP) and pyruvate dehydrogenase complex enzyme <em>DLAT E2</em>, without altering lactate secretion. This metabolic rewiring of trophoblast cells induced by VIP takes place without compromising mitochondrial function or reactive oxygen species (ROS) production. Moreover, cytotrophoblast cell migration induced by VIP required the three glycolysis, oxidative phosphorylation (OXPHOS) and FAO pathways. Our results provide evidence supporting VIP as a metabolic regulatory peptide in cytotrophoblast cells sustaining proper placentation and fetal growth.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 2","pages":"Article 119886"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799316","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":"A fluorescent protein C-terminal fusion knock-in is functional with TRPA1 but not TRPC5","authors":"Aaron Tragl ,&nbsp;Alexandra Ptakova ,&nbsp;Viktor Sinica ,&nbsp;Rathej Meerupally ,&nbsp;Christine König ,&nbsp;Carolina Roza ,&nbsp;Ivan Barvík ,&nbsp;Viktorie Vlachova ,&nbsp;Katharina Zimmermann","doi":"10.1016/j.bbamcr.2024.119887","DOIUrl":"10.1016/j.bbamcr.2024.119887","url":null,"abstract":"<div><h3>Objective</h3><div>Transgenic mice with fluorescent protein (FP) reporters take full advantage of new <em>in vivo</em> imaging technologies. Therefore, we generated a TRPC5- and a TRPA1-reporter mouse based on FP C-terminal fusion, providing us with better alternatives for studying the physiology, interaction and coeffectors of these two TRP channels at the cellular and tissue level.</div></div><div><h3>Methods</h3><div>We generated transgenic constructs of the murine TRPC5- and TRPA1-gene with a 3*GGGGS linker and C-terminal fusion to mCherry and mTagBFP, respectively. We microinjected zygotes to generate reporter mice. Reporter mice were examined for visible fluorescence in trigeminal ganglia with two-photon microscopy, immunohistochemistry and calcium imaging.</div></div><div><h3>Results</h3><div>Both TRPC5-mCherry and TRPA1-mTagBFP knock-in mouse models were successful at the DNA and RNA level. However, at the protein level, TRPC5 resulted in no mCherry fluorescence. In contrast, sensory neurons derived from the TRPA1-reporter mice exhibited visible mTag-BFP fluorescence, although TRPA1 had apparently lost its ion channel function.</div></div><div><h3>Conclusions</h3><div>Creating transgenic mice with a TRP channel tagged at the C-terminus with a FP requires detailed investigation of the structural and functional consequences in a given cellular context and fine-tuning the design of specific constructs for a given TRP channel subtype. Different degrees of functional impairment of TRPA1 and TRPC5 constructs suggest a specific importance of the distal C-terminus for the regulation of these two channels in trigeminal neurons.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 2","pages":"Article 119887"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812111","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":"Blockage of polycystin-2 alleviates myocardial ischemia/reperfusion injury by inhibiting autophagy through the Ca2+/Akt/Beclin 1 pathway","authors":"Xiao-dan Qin ,&nbsp;Jian-feng Liang ,&nbsp;Lin-yu Gan ,&nbsp;Ke-shan Peng ,&nbsp;Xue-hong Huang ,&nbsp;Xiao-ting Li ,&nbsp;Jin-li Chen ,&nbsp;Wan Li ,&nbsp;Lei Zhang ,&nbsp;Jie Jian ,&nbsp;Jun Lu","doi":"10.1016/j.bbamcr.2024.119892","DOIUrl":"10.1016/j.bbamcr.2024.119892","url":null,"abstract":"<div><div>Autophagy is a well-conserved self-protection process that plays an important role in cardiovascular diseases. Excessive autophagy during myocardial ischemia/reperfusion injury (MIRI) induces calcium overload and the overactivation of an autophagic response, thereby aggravating cardiomyocyte damage. Polycystin-2 (PC2) is a Ca²⁺-permeable nonselective cation channel implicated in the regulation of autophagy. In the present study, autophagy was upregulated in myocardial ischemia/reperfusion <em>in vivo</em> and <em>in vitro</em>. PC2 knockdown using adeno-associated virus 9 particles containing <em>Pkd2</em> short hairpin RNA infection markedly ameliorated MIRI, evidenced by reduced infarct size, diminished morphological changes, decreased cTnI levels, and improved cardiac function. Silencing PC2 reduced the autophagic flux in H9c2 cells. PC2 overexpression-mediated autophagic flux was inhibited by intracellular Ca²⁺ chelation with BAPTA-AM. Furthermore, PC2 ablation upregulated p-Akt (Ser473) and downregulated Beclin 1 in H/R. BAPTA-AM downregulated p-Akt(Ser473) and upregulated Beclin 1in PC2-overexpressing H9c2 cells. Moreover, the Akt inhibitor MK2206 abolished the BAPTA-AM-blunted PC2-dependent control of autophagy. Collectively, these results indicated that blockade of PC2 may be associated with the Ca²⁺/Akt/Beclin 1 signaling, thereby inhibiting excessive autophagy and serving as a potential strategy for mitigating MIRI.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 2","pages":"Article 119892"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845665","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":"Fidgetin binds spastin to attenuate the microtubule-severing activity","authors":"Ying Sun ,&nbsp;Skandha Ramakrishnan ,&nbsp;Xiaona Lai ,&nbsp;Ronghua Wu ,&nbsp;Zhangji Dong ,&nbsp;Liang Qiang ,&nbsp;Mei Liu","doi":"10.1016/j.bbamcr.2024.119890","DOIUrl":"10.1016/j.bbamcr.2024.119890","url":null,"abstract":"<div><div>Microtubule-severing enzymes such as spastin, katanin, and fidgetin, characterized by their AAA ATPase domains, are pivotal in modulating microtubule dynamics and behavior across various cellular processes. While spastin and katanin are recognized for their predominant and robust severing of stable microtubules, thereby enhancing microtubule turnover, fidgetin exhibits comparatively weaker severing activity and selectively targets labile microtubules. The interplay among these enzymes and their mutual regulatory mechanisms remains inadequately understood. In this study, we elucidate the functional interaction between spastin and fidgetin, focusing on their roles in microtubule severing and neurite outgrowth. Our findings demonstrate that fidgetin serves as a negative regulator of spastin's severing activity. Co-expression assays revealed that fidgetin significantly attenuates spastin's severing efficiency, as confirmed by fluorescence-based microtubule polymerization assays and quantitative imaging of microtubule dynamics. Co-immunoprecipitation and Förster Resonance Energy Transfer (FRET) analyses further established a direct interaction between fidgetin and spastin, suggesting that fidgetin modulates spastin's activity through direct binding, possibly contributing to forming the hetero-hexmeric ring for their severing activities. Functionally, spastin overexpression in neuronal cells enhances neurite outgrowth, an effect that is suppressed upon co-expression with fidgetin, indicating that fidgetin counterbalances spastin's activity to regulate neurite extension. Therefore, this study uncovers a previously unrecognized mechanism by which fidgetin modulates spastin's function, providing critical insights into the intricate regulation of microtubule severing. These findings have significant implications for therapeutic strategies targeting microtubule-severing activities, particularly in neurodevelopmental and neurodegenerative disorders where microtubule dysregulation is a hallmark.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 2","pages":"Article 119890"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833545","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":"GALNT6, transcriptionally inhibited by KLF9, promotes osteosarcoma progression by increasing EFEMP1 expression via O-glycosylation modification","authors":"Ziyuan Tong,&nbsp;Yuan Shen,&nbsp;Quan Yuan,&nbsp;Honghao Yu","doi":"10.1016/j.bbamcr.2024.119879","DOIUrl":"10.1016/j.bbamcr.2024.119879","url":null,"abstract":"<div><div>Osteosarcoma (OS) is one of the deadliest malignancies in adolescents and its treatment status and prognosis remain unsatisfactory. <em>N</em>-acetylgalactosamine transferase 6 (GALNT6), one of the key enzymes regulating O-glycosylation, functions vary in different types of cancer. Currently, the function of GALNT6 in OS is unclear. Our results showed that GALNT6 was highly expressed in OS tissues, and the patients with higher GALNT6 expression exhibited a lower overall survival rate than patients with lower GALNT6 expression. We constructed the GALNT6-knockdown and GALNT6-overexpression vectors based on Tet-on system and packaged lentiviral particles to modulate GALNT6 expression. GALNT6 silencing impaired OC cell growth and metastasis both <em>in vivo</em> and <em>vitro</em>. Kruppel-like factor 9 (KLF9), a transcription factor known to suppress OS progression, was found to block GALNT6 transcription by binding to its promoter. Meanwhile, GALNT6 overexpression restored the effects caused by KLF9 upregulation. GALNT6 was known to affect protein stability by O-glycosylation regulation, thus the label-free proteomics combined with co-immunoprecipitation/mass-spectrum (MS) analysis were conducted to identify the potential mechanism of GALNT6 in promoting OS progression. EGF-containing fibulin extracellular matrix protein 1 (EFEMP1), contained several O-glycosylation sites and was upregulated in GALNT6 overexpressing cells (Log₂FC = 1.3195, <em>p</em> = 0.0160), attracted our attention. We demonstrated that GALNT6 interacted with EFEMP1 at protein level. The O-glycosylation of EFEMP1 was increased by GALNT6 overexpression, which slowed the degradation rate of EFEMP1. EFEMP1 knockdown reversed the effects of GALNT6 overexpression. Collectively, our observations demonstrate that KLF9/GALNT6/EFEMP1 may be a promising direction for OS treatment.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 2","pages":"Article 119879"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709129","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":"DOCK2 deficiency alleviates neuroinflammation and affords neuroprotection after spinal cord injury","authors":"Haocong Zhang,&nbsp;Liangbi Xiang,&nbsp;Hong Yuan,&nbsp;Hailong Yu","doi":"10.1016/j.bbamcr.2024.119882","DOIUrl":"10.1016/j.bbamcr.2024.119882","url":null,"abstract":"<div><div>Neuroinflammation-caused secondary injury is a key event after spinal cord injury (SCI). Dedicator of cytokinesis 2 (DOCK2) belonging to DOCK-A subfamily has a vital role in microglia polarization and neuroinflammation via mediating Rac activation. However, the role of DOCK2 in SCI is unclear. In the present study, SCI model in mice was established by an impactor at thoracic T10 level. DOCK2 expression was significantly increased in the spinal cord after SCI. After knocking down DOCK2 using a lentivirus-mediated method, SCI mice exhibited improved motor function recovery, as revealed by increased Basso Mouse Scale (BMS) score, angle of incline, and relatively coordinated footprint, and decreased damaged area in the spinal cord. DOCK2 deficiency reduced neuronal apoptosis in the spinal cord after injury. Besides, deficiency of DOCK2 suppressed neuroinflammation after SCI, demonstrated by the reduction in pro-inflammatory mediators including IFN-γ, IL-1β and IL-6 and the increase in IL-4, IL-10 and IL-13, anti-inflammatory factors. The CD86, iNOS and COX-2 were down-regulated in the spinal cord, whereas CD206, Arg-1 and TGF-β were up-regulated by DOCK2 deficiency. Rac activation was prevented by DOCK2 deficiency following SCI. In vitro experiments were conducted for further verification. Treatment of BV-2 microglia with lentivirus-mediated DOCK2 inhibited IFN-γ/LPS-induced pro-inflammatory microglia polarization but increased IL-4-induced anti-inflammatory microglia, through inhibiting Rac activation. In brief, our data reveal that DOCK2 deficiency improves functional recovery in mice after SCI, which is related to Rac activation.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 2","pages":"Article 119882"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738279","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":"Hypoxia enhances IL-8 signaling through inhibiting miR-128-3p expression in glioblastomas","authors":"Kuo-Hao Ho ,&nbsp;Shao-Yuan Hsu ,&nbsp;Peng-Hsu Chen ,&nbsp;Chia-Hsiung Cheng ,&nbsp;Ann-Jeng Liu ,&nbsp;Ming-Hsien Chien ,&nbsp;Ku-Chung Chen","doi":"10.1016/j.bbamcr.2024.119885","DOIUrl":"10.1016/j.bbamcr.2024.119885","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM) is an aggressive type of brain tumor known for its hypoxic microenvironment. Understanding the dysregulated mechanisms in hypoxic GBM is crucial for its effective treatment. Through data mining of The Cancer Genome Atlas (TCGA) with hypoxia enrichment scores and in vitro experiments, miR-128-3p was negatively correlated with hypoxia signaling and the epithelial-mesenchymal transition (EMT). Additionally, lower miR-128-3p levels existed in hypoxic GBM, leading to desensitizing temozolomide (TMZ)'s efficacy, a first-line therapeutic drug for GBM. Overexpressing miR-128-3p enhanced both the in vitro and in vivo sensitivity of hypoxic gliomas to TMZ treatment. Mechanistically, HIF-1α suppressed miR-128-3p expression in hypoxic GBM. Through establishing miR-128-3p-mediated transcriptomic profiles and data mining, interleukin (IL)-8 was selected. IL-8 respectively showed positive and negative correlations with hypoxia and miR-128-3p, and was associated with poor TMZ therapeutic results in GBM. Elevated miR-128-3p, which targets both the 3′-untranslated region (UTR) and 5′UTR of IL-8, resulted in suppression of IL-8 expression. Moreover, IL-8 was validated to be involved in HIF-1α/miR-128-3p-regulated TMZ sensitivity and the EMT in hypoxic GBM cells. Collectively, the HIF-1α/miR-128-3p/IL-8 signaling pathway plays a critical role in promoting the progression of hypoxic GBM. Targeting this signaling pathway holds promise as a potential therapeutic strategy.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 2","pages":"Article 119885"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779305","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}