Biochimica et biophysica acta. Molecular cell research最新文献

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Blockage of polycystin-2 alleviates myocardial ischemia/reperfusion injury by inhibiting autophagy through the Ca2+/Akt/Beclin 1 pathway. 通过Ca2+/Akt/Beclin 1途径抑制自噬,阻断多囊卵巢素-2可减轻心肌缺血再灌注损伤。
IF 4.6 2区 生物学
Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-12-16 DOI: 10.1016/j.bbamcr.2024.119892
Xiao-Dan Qin, Jian-Feng Liang, Lin-Yu Gan, Ke-Shan Peng, Xue-Hong Huang, Xiao-Ting Li, Jin-Li Chen, Wan Li, Lei Zhang, Jie Jian, Jun Lu
{"title":"Blockage of polycystin-2 alleviates myocardial ischemia/reperfusion injury by inhibiting autophagy through the Ca<sup>2+</sup>/Akt/Beclin 1 pathway.","authors":"Xiao-Dan Qin, Jian-Feng Liang, Lin-Yu Gan, Ke-Shan Peng, Xue-Hong Huang, Xiao-Ting Li, Jin-Li Chen, Wan Li, Lei Zhang, Jie Jian, Jun Lu","doi":"10.1016/j.bbamcr.2024.119892","DOIUrl":"10.1016/j.bbamcr.2024.119892","url":null,"abstract":"<p><p>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 Ca<sup>2+</sup>-permeable nonselective cation channel implicated in the regulation of autophagy. In the present study, autophagy was upregulated in myocardial ischemia/reperfusion in vivo and in vitro. PC2 knockdown using adeno-associated virus 9 particles containing Pkd2 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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup>/Akt/Beclin 1 signaling, thereby inhibiting excessive autophagy and serving as a potential strategy for mitigating MIRI.</p>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":" ","pages":"119892"},"PeriodicalIF":4.6,"publicationDate":"2024-12-16","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}
引用次数: 0
Hornerin expressed on endothelial cells via interacting with thrombomodulin modulates vascular inflammation and angiogenesis.
IF 4.6 2区 生物学
Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-12-15 DOI: 10.1016/j.bbamcr.2024.119891
Takayuki Okamoto, Mai Hattori, Yukiko Katsube, Junichi Ota, Kunihiro Asanuma, Haruki Usuda, Koichiro Wada, Koji Suzuki, Tetsuro Nikai
{"title":"Hornerin expressed on endothelial cells via interacting with thrombomodulin modulates vascular inflammation and angiogenesis.","authors":"Takayuki Okamoto, Mai Hattori, Yukiko Katsube, Junichi Ota, Kunihiro Asanuma, Haruki Usuda, Koichiro Wada, Koji Suzuki, Tetsuro Nikai","doi":"10.1016/j.bbamcr.2024.119891","DOIUrl":"10.1016/j.bbamcr.2024.119891","url":null,"abstract":"<p><p>Thrombomodulin is predominantly expressed on vascular endothelial cells and modulates endothelial cell functions by interacting with multiple ligands. The specific thrombomodulin receptor or cofactor active on the endothelial cell surface remains elusive. This study aims to identify interacting partners of thrombomodulin on endothelial cells. Here, using a liquid chromatograph-tandem mass spectrometer, hornerin was identified as a candidate protein. We then investigated hornerin protein and mRNA expression in endothelial cells. Hornerin protein was detected in the mouse endothelium of the aorta and lung. Both human- and mouse-cultured endothelial cells expressed hornerin mRNA and protein. Moreover, immunoprecipitation analysis suggested the direct protein interaction between thrombomodulin and hornerin. Lipopolysaccharides administration increased serum hornerin concentrations in mice and reduced hornerin protein levels on the surface of cultured endothelial cells as same as thrombomodulin protein. Thrombomodulin-targeting siRNA decreased not only thrombomodulin protein levels but also hornerin protein levels in cultured endothelial cells. Thrombomodulin- or hornerin-targeting siRNA impaired tube formation and leukocyte adhesion to endothelial cells. Our findings reveal that hornerin is located on vascular endothelial cells in the presence of thrombomodulin and suggest that endothelial thrombomodulin and hornerin may interact, which may play an important role in endothelial cell functions such as vascular inflammation and angiogenesis.</p>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":" ","pages":"119891"},"PeriodicalIF":4.6,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845666","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}
引用次数: 0
Fidgetin binds spastin to attenuate the microtubule-severing activity.
IF 4.6 2区 生物学
Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-12-15 DOI: 10.1016/j.bbamcr.2024.119890
Ying Sun, Skandha Ramakrishnan, Xiaona Lai, Ronghua Wu, Zhangji Dong, Liang Qiang, Mei Liu
{"title":"Fidgetin binds spastin to attenuate the microtubule-severing activity.","authors":"Ying Sun, Skandha Ramakrishnan, Xiaona Lai, Ronghua Wu, Zhangji Dong, Liang Qiang, Mei Liu","doi":"10.1016/j.bbamcr.2024.119890","DOIUrl":"10.1016/j.bbamcr.2024.119890","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":" ","pages":"119890"},"PeriodicalIF":4.6,"publicationDate":"2024-12-15","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}
引用次数: 0
Functional analysis of yak alveolar type II epithelial cells at high and low altitudes based on single-cell sequencing.
IF 4.6 2区 生物学
Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-12-15 DOI: 10.1016/j.bbamcr.2024.119889
Jingyi Li, Nating Huang, Xun Zhang, Huizhen Wang, Jiarui Chen, Qing Wei
{"title":"Functional analysis of yak alveolar type II epithelial cells at high and low altitudes based on single-cell sequencing.","authors":"Jingyi Li, Nating Huang, Xun Zhang, Huizhen Wang, Jiarui Chen, Qing Wei","doi":"10.1016/j.bbamcr.2024.119889","DOIUrl":"10.1016/j.bbamcr.2024.119889","url":null,"abstract":"<p><p>The adaptation of lung cells to high-altitude environments represents a notable gap in our understanding of how animals cope with hypoxic conditions. Alveolar epithelial cells type II (AEC II) are crucial for lung development and repair. However, their, specific role in the adaptation of yaks to high-altitude environments remains unclear. In this study, we aimed to address this gap by investigating the differential responses of AEC II in yaks at high and low altitudes (4000 m and 2600 m, respectively). We used the 10 × scRNA-seq technology to construct a comprehensive cell atlas of yak lung tissue, and identified 15 distinct cell classes. AEC II in high-altitude yaks revealed increased immunomodulatory, adhesive, and metabolic activities, which are crucial for maintaining lung tissue stability and energy supply under hypoxic conditions. Furthermore, alveolar epithelial progenitor cells within AEC II can differentiate into both Alveolar epithelial cell type I (AEC I) and AEC II. SHIP1 and other factors are promoters of AEC I transdifferentiation, whereas SFTPC and others promote AEC II transdifferentiation. This study provides new insights into the evolutionary adaptation of lung cells in plateau animals by elucidating the molecular mechanisms underlying AEC II adaptation to high-altitude environments.</p>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":" ","pages":"119889"},"PeriodicalIF":4.6,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833691","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}
引用次数: 0
RANKL regulates differentially breast cancer stem cell properties through its RANK and LGR4 receptors.
IF 4.6 2区 生物学
Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-12-09 DOI: 10.1016/j.bbamcr.2024.119888
Alejandro Ordaz-Ramos, Jorge Diaz-Blancas, Aketzalli Martínez-Cruz, Rosario Castro-Oropeza, Cecilia Zampedri, Damaris P Romero-Rodríguez, Mauricio Rodriguez-Dorantes, Jorge Melendez-Zajgla, Vilma Maldonado, Karla Vazquez-Santillan
{"title":"RANKL regulates differentially breast cancer stem cell properties through its RANK and LGR4 receptors.","authors":"Alejandro Ordaz-Ramos, Jorge Diaz-Blancas, Aketzalli Martínez-Cruz, Rosario Castro-Oropeza, Cecilia Zampedri, Damaris P Romero-Rodríguez, Mauricio Rodriguez-Dorantes, Jorge Melendez-Zajgla, Vilma Maldonado, Karla Vazquez-Santillan","doi":"10.1016/j.bbamcr.2024.119888","DOIUrl":"10.1016/j.bbamcr.2024.119888","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>This project aimed to elucidate the role of RANKL in regulating stemness depending on the expression of its receptors.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Our findings suggest that RANKL exerts different responses according to the expression of its receptors.</p>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":" ","pages":"119888"},"PeriodicalIF":4.6,"publicationDate":"2024-12-09","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A fluorescent protein C-terminal fusion knock-in is functional with TRPA1 but not TRPC5.
IF 4.6 2区 生物学
Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-12-09 DOI: 10.1016/j.bbamcr.2024.119887
Aaron Tragl, Alexandra Ptakova, Viktor Sinica, Rathej Meerupally, Christine König, Carolina Roza, Ivan Barvík, Viktorie Vlachova, Katharina Zimmermann
{"title":"A fluorescent protein C-terminal fusion knock-in is functional with TRPA1 but not TRPC5.","authors":"Aaron Tragl, Alexandra Ptakova, Viktor Sinica, Rathej Meerupally, Christine König, Carolina Roza, Ivan Barvík, Viktorie Vlachova, Katharina Zimmermann","doi":"10.1016/j.bbamcr.2024.119887","DOIUrl":"10.1016/j.bbamcr.2024.119887","url":null,"abstract":"<p><strong>Objective: </strong>Transgenic mice with fluorescent protein (FP) reporters take full advantage of new in vivo 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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":" ","pages":"119887"},"PeriodicalIF":4.6,"publicationDate":"2024-12-09","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vasoactive intestinal peptide induces metabolic rewiring of human-derived cytotrophoblast cells to promote cell migration.
IF 4.6 2区 生物学
Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-12-07 DOI: 10.1016/j.bbamcr.2024.119886
Fátima Merech, Brenda Lara, Daiana Rios, Daniel Paparini, Rosanna Ramhorst, Vanesa Hauk, Claudia Pérez Leirós, Daiana Vota
{"title":"Vasoactive intestinal peptide induces metabolic rewiring of human-derived cytotrophoblast cells to promote cell migration.","authors":"Fátima Merech, Brenda Lara, Daiana Rios, Daniel Paparini, Rosanna Ramhorst, Vanesa Hauk, Claudia Pérez Leirós, Daiana Vota","doi":"10.1016/j.bbamcr.2024.119886","DOIUrl":"10.1016/j.bbamcr.2024.119886","url":null,"abstract":"<p><p>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 FATP2 transporter, CPT1 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 DLAT E2, 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.</p>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":" ","pages":"119886"},"PeriodicalIF":4.6,"publicationDate":"2024-12-07","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}
引用次数: 0
Hypoxia enhances IL-8 signaling through inhibiting miR-128-3p expression in glioblastomas.
IF 4.6 2区 生物学
Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-12-02 DOI: 10.1016/j.bbamcr.2024.119885
Kuo-Hao Ho, Shao-Yuan Hsu, Peng-Hsu Chen, Chia-Hsiung Cheng, Ann-Jeng Liu, Ming-Hsien Chien, Ku-Chung Chen
{"title":"Hypoxia enhances IL-8 signaling through inhibiting miR-128-3p expression in glioblastomas.","authors":"Kuo-Hao Ho, Shao-Yuan Hsu, Peng-Hsu Chen, Chia-Hsiung Cheng, Ann-Jeng Liu, Ming-Hsien Chien, Ku-Chung Chen","doi":"10.1016/j.bbamcr.2024.119885","DOIUrl":"10.1016/j.bbamcr.2024.119885","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":" ","pages":"119885"},"PeriodicalIF":4.6,"publicationDate":"2024-12-02","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}
引用次数: 0
Enhanced radiotherapy susceptibility in NSCLC through palbociclib-mediated PP5 inhibition.
IF 4.6 2区 生物学
Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-11-30 DOI: 10.1016/j.bbamcr.2024.119884
Chao-Yuan Huang, Li-Ju Chen, Grace Chen, Cheng-Yi Wang, Shiao-Ya Hong
{"title":"Enhanced radiotherapy susceptibility in NSCLC through palbociclib-mediated PP5 inhibition.","authors":"Chao-Yuan Huang, Li-Ju Chen, Grace Chen, Cheng-Yi Wang, Shiao-Ya Hong","doi":"10.1016/j.bbamcr.2024.119884","DOIUrl":"10.1016/j.bbamcr.2024.119884","url":null,"abstract":"<p><p>Radiotherapy remains a cornerstone in the treatment of non-small cell lung cancer (NSCLC), yet radioresistance often limits its efficacy. Identifying molecular targets that enhance radiosensitivity is crucial to offering both curative and palliative benefits for patients with NSCLC. Utilizing bioinformatics analysis, our study revealed significantly higher expression of PP5 in NSCLC tissues compared to normal tissues. Kaplan-Meier survival analysis also showed that high PP5 expression correlates with poorer overall survival, particularly in patients undergoing radiotherapy, suggesting a role for PP5 in radioresistance. We further demonstrated that PP5 is a critical target of palbociclib, distinct from CDK4/6, influencing radiosensitivity in NSCLC. Palbociclib enhanced radiotherapy susceptibility by inducing sustained DNA damage and AMPK activation. The subsequent cellular event is apoptosis rather than autophagy. Furthermore, the enhanced efficacy of combination therapy was counteracted by an AMPK inhibitor and PP5 activator, underscoring the importance of these pathways in mediating the response. Our findings provide compelling evidence that targeting PP5 can significantly enhance the therapeutic outcomes of radiotherapy in NSCLC. This research offers valuable insights into new combination therapy strategies, highlighting the potential of PP5 as a novel therapeutic target to overcome radioresistance.</p>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":" ","pages":"119884"},"PeriodicalIF":4.6,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765995","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}
引用次数: 0
The loss of keratin 77 in murine skin is functionally compensated by keratin 1 小鼠皮肤角蛋白 77 的缺失可由角蛋白 1 进行功能补偿
IF 4.6 2区 生物学
Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-11-26 DOI: 10.1016/j.bbamcr.2024.119881
S. Ghorbanalipoor , T. Hommel , T. Kolbe , T. Fröhlich , B. Wagner , C. Posch , M. Dahlhoff
{"title":"The loss of keratin 77 in murine skin is functionally compensated by keratin 1","authors":"S. Ghorbanalipoor ,&nbsp;T. Hommel ,&nbsp;T. Kolbe ,&nbsp;T. Fröhlich ,&nbsp;B. Wagner ,&nbsp;C. Posch ,&nbsp;M. Dahlhoff","doi":"10.1016/j.bbamcr.2024.119881","DOIUrl":"10.1016/j.bbamcr.2024.119881","url":null,"abstract":"<div><div>Keratins, the intermediate filament-forming proteins of the epithelial cells, are mainly expressed in keratinocytes, preserving the structural integrity and cohesion of the epidermis. There are multiple inherited skin conditions arising from mutations in the encoding genes of specific keratins, highlighting their significance in skin health. Furthermore, the aberrant expression of keratins is evidenced in certain skin diseases, such as psoriasis, atopic dermatitis, and skin cancer. Keratin 77 (KRT77) is a type II keratin with demonstrated expression in human and mouse sweat glands' ducts. Using the CRISPR/Cas9 technique, we generated a <em>Krt77</em>-deficient (<em>Krt77</em>-KO) mouse line to reveal its obscure function in skin biology and homeostasis. KRT77 loss did not result in any fetal lethality or detrimental impact on the development of the skin and its appendages. However, we identified a substantially increased expression of KRT1 in the skin of the <em>Krt77</em>-KO mouse line in comparison with control littermates at both mRNA and protein levels using RT-qPCR and western blot analyses, respectively. Based on these findings, we concluded that the absence of KRT77 in the murine skin leads to upregulation of KRT1, an alternative epidermal type II keratin within the same subfamily as KRT77, which rescues the lack of KRT77.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 2","pages":"Article 119881"},"PeriodicalIF":4.6,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142723916","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}
引用次数: 0
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