641. Renal Expression Levels of C5a Receptor and Autophagy-related Beclin-1 and LC3A/B Are Simultaneously Enhanced Under Immunoglobulin Treatment in a Rat Model of Sepsis.
作者: Özlem Polat.;Gunseli Orhun.;Ilkay Anakli.;Vuslat Yilmaz.;Gizem Koral.;Canan Ulusoy.;Mert Canbaz.;Perihan Ergin Ozcan.;Erdem Tüzün.;Figen Esen.
来源: In Vivo. 2025年39卷2期810-818页
Sepsis-induced acute kidney injury is a fatal, potentially reversible clinical condition. C5a receptor (C5aR) has been implied to play pivotal roles in both autophagy and sepsis-induced organ dysfunction. The aim of this study was to demonstrate the effects of intravenous immunoglobulin preparations on the expression of autophagy markers and investigate possible association between C5aR expression and autophagy in the kidney tissue of septic rats.
642. Imipramine-induced Apoptosis and Metastasis Inhibition in Human Bladder Cancer T24 Cells Through EGFR/ERK/NF-κB Pathway Suppression.
作者: Wei-Shu Wang.;Yu-Chang Liu.;Tsai-Lin Lo.;Fei-Ting Hsu.;Chih-Hung Chiang.
来源: In Vivo. 2025年39卷2期669-682页
Bladder cancer is a prevalent malignancy, ranging from superficial forms to more aggressive types that invade the muscle and require extensive treatment. Imipramine, traditionally used as an antidepressant, has shown potential as an anti-cancer agent.
643. Scutellarin mitigates high glucose-induced pyroptosis in diabetic atherosclerosis: Role of Nrf2-FBXL2-mediated NLRP3 degradation.
作者: Qingxin Meng.;Yongpan Huang.;Xian Long.;Lijing Liu.;Yani Tang.;Jingjing He.;Yayuan Luo.
来源: Endocr J. 2025年72卷5期495-507页
This study investigated the role of scutellarin (Scu) and Nrf2 in diabetic atherosclerosis, focusing on their effects on FBXL2 and NLRP3 ubiquitination. Human umbilical vein endothelial cells were treated with high glucose (HG) to model diabetic atherosclerosis in vitro. Cell viability, cytotoxicity, pyroptosis, and inflammatory cytokine levels were assessed, and gene interactions were examined by dual-luciferase reporter assays. Ubiquitination and protein levels were analyzed through immunoprecipitation and western blotting. The results revealed that HG treatment decreased Nrf2 and FBXL2 levels and enhanced NLRP3-mediated pyroptosis. However, Scu treatment increased Nrf2 expression, improved cell viability, and inhibited pyroptosis. Nrf2 knockdown downregulated FBXL2 and reversed the protective effects of Scu. Additionally, FBXL2 promoted the ubiquitination-mediated degradation of NLRP3 and suppressed pyroptosis. The activation of NLRP3 reversed the protective effects of Scu on diabetic atherosclerosis. These findings suggest that Scu alleviated diabetic atherosclerosis by increasing Nrf2 and FBXL2 expression, promoting NLRP3 ubiquitination-mediated degradation, and suppressing pyroptosis.
644. A role for NFIB in SOX2 downregulation and epigenome accessibility changes due to long-term estrogen treatment of breast cancer epithelial cells.
作者: Luis E Abatti.;Zoe E Gillespie.;Patricia Lado-Fernández.;Manuel Collado.;Jennifer A Mitchell.
来源: Biochem Cell Biol. 2025年103卷1-14页
Estrogen (E2) regulates the differentiation and proliferation of mammary progenitor cells by modulating the transcription of multiple genes. One of the genes that is downregulated by E2 is SOX2, a transcription factor associated with stem and progenitor cells that is overexpressed during breast tumourigenesis. To elucidate the mechanisms underlying E2-mediated SOX2 repression, we investigated epigenome and transcriptome changes following short- and long-term E2 exposure in breast cancer cells. We found that short-term E2 exposure reduces chromatin accessibility at the downstream SOX2 SRR134 enhancer, decreasing SOX2 expression. In contrast, long-term E2 exposure completely represses SOX2 transcription while maintaining accessibility at the SRR124-134 enhancer cluster, keeping it poised for reactivation. This repression was accompanied by widespread epigenome and transcriptome changes associated with commitment towards a more differentiated and less invasive luminal phenotype. Finally, we identified a role for the transcription factor NFIB in this process, suggesting it collaborates with the estrogen receptor to mediate SOX2 repression and genome-wide epigenome accessibility changes.
645. Modulation of blood-tumor barrier transcriptional programs improves intratumoral drug delivery and potentiates chemotherapy in GBM.
作者: Jorge L Jimenez-Macias.;Philippa Vaughn-Beaucaire.;Ayush Bharati.;Zheyun Xu.;Megan Forrest.;Jason Hong.;Michael Sun.;Andrea Schmidt.;Jasmine Clark.;William Hawkins.;Noe Mercado.;Jacqueline Real.;Kelsey Huntington.;Mykola Zdioruk.;Michal O Nowicki.;Choi-Fong Cho.;Bin Wu.;Weiyi Li.;Theresa Logan.;Katherine E Manz.;Kurt D Pennell.;Bogdan I Fedeles.;Paul Bertone.;Michael Punsoni.;Alexander S Brodsky.;Sean E Lawler.
来源: Sci Adv. 2025年11卷9期eadr1481页
Efficient drug delivery to glioblastoma (GBM) is a major obstacle as the blood-brain barrier (BBB) and the blood-tumor barrier (BTB) prevent passage of the majority of chemotherapies into the brain. Here, we identified a transcriptional 12-gene signature associated with the BTB in GBM. We identified CDH5 as a core molecule in this set and confirmed its expression in GBM vasculature using transcriptomics and immunostaining of patient specimens. The indirubin-derivative, 6-bromoindirubin acetoxime (BIA), down-regulates CDH5 and other BTB signature genes, causing endothelial barrier disruption in vitro and in murine GBM xenograft models. Treatment with BIA increased intratumoral cisplatin accumulation and potentiated DNA damage by targeting DNA repair pathways. Last, using an injectable BIA nanoparticle formulation, PPRX-1701, we significantly improved cisplatin efficacy in murine GBM. Our work reveals potential targets of the BTB and the bifunctional properties of BIA as a BTB modulator and a potentiator of chemotherapy, supporting its further development.
646. Radiation-induced cellular plasticity primes glioblastoma for forskolin-mediated differentiation.
作者: Ling He.;Daria Azizad.;Kruttika Bhat.;Angeliki Ioannidis.;Carter J Hoffmann.;Evelyn Arambula.;Mansoureh Eghbali.;Aparna Bhaduri.;Harley I Kornblum.;Frank Pajonk.
来源: Proc Natl Acad Sci U S A. 2025年122卷9期e2415557122页
Glioblastoma (GBM) is the deadliest brain cancer in adults, and all patients succumb to the tumor. While surgery followed by chemoradiotherapy delays disease progression, these treatments do not lead to tumor control, and targeted therapies or biologics have failed to further improve survival. Utilizing a transient radiation-induced state of multipotency, we used the adenylcyclase activator forskolin to alter the fate of irradiated glioma cells. The effects of the combined treatment on neuronal marker expression, cell cycle distribution, and proliferation were studied. Gene expression profiling was conducted using bulk RNA-seq. Changes in cell populations were investigated using single-cell RNA-seq. Effects on glioma stem cells (GSCs) were studied in extreme limiting dilution assays, and the effects on median survival were studied in both syngeneic and PDOX mouse models of GBM. The combined treatment induced the expression of neuronal markers in glioma cells, reduced proliferation, and led to a distinct gene expression profile. scRNA-seq revealed that the combined treatment forced glioma cells into a microglia- and neuron-like phenotype. In vivo, this treatment led to a loss of GSCs and prolonged median survival. Collectively, our data suggest that revisiting a differentiation therapy with forskolin in combination with radiation could lead to clinical benefit.
647. Cordycepin mediates pyroptosis in HCC through the upregulation of TXNIP and synergizes with anti-PD-L1 immunotherapy.
作者: Bu-Gang Liang.;Yi-Min Zheng.;Hong-Ye Shen.;Guo-Huan Yang.;Wen-Xin Xu.;Chang-Jun Tan.;Ai-Wu Ke.;Wen-Zheng Qin.
来源: Hepatol Commun. 2025年9卷3期
Immune checkpoint inhibitors are effective treatments for HCC; however, their therapeutic efficacy is often limited by the development of drug resistance. Therefore, investigating new combination therapeutics involving immune checkpoint inhibitors is critical to improving patient prognosis. In this study, we investigated the therapeutic effect of cordycepin (COR) in HCC and its synergistic effect with anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy.
648. Synthesis and evaluation of 5, 6-dihydro-8H-isoquinolino[1, 2-b]quinazolin-8-one derivatives as novel non-lipogenic ABCA1 up-regulators with inhibitory effects on macrophage-derived foam cell formation.
作者: Changhuan Yang.;Lin Chen.;Yanmei Jiang.;Demeng Sun.;Yun Hu.
来源: J Enzyme Inhib Med Chem. 2025年40卷1期2470310页
Increasing the expression of ATP-binding cassette transporter A1 (ABCA1) can lower cellular cholesterol levels and prevent foam cell formation. In this study, a series of 5, 6-dihydro-8H-isoquinolino[1, 2-b]quinazolin-8-one derivatives were synthesised and assessed for their ability to up-regulate ABCA1 expression. The structure-activity relationship was explored and summarised. Among the 28 derivatives, compound 3 exhibited the most potent activity in activating the ABCA1 promoter (2.50-fold), significantly up-regulating both ABCA1 mRNA and protein levels in RAW264.7 macrophage cells. Mechanism studies revealed that compound 3 acted by targeting the LXR-involved pathway. In a foam cell model, compound 3 reduced ox-LDL-induced lipid accumulation and thereby inhibited foam cell formation. Moreover, compared to the LXR agonist T0901317, compound 3 led to minimal accumulation of unwanted lipids and triglycerides in HepG2 cells. With little cytotoxicity towards all the tested cell lines, compound 3 holds promise as a novel potential anti-atherogenic agent for further exploration.
649. The IGF2BP1 oncogene is a druggable m6A-dependent enhancer of YAP1-driven gene expression in ovarian cancer.
作者: Annekatrin Schott.;Theresa Simon.;Simon Müller.;Alexander Rausch.;Bianca Busch.;Markus Glaß.;Danny Misiak.;Mohammad Dipto.;Hend Elrewany.;Lara Meret Peters.;Sunita Tripathee.;Ehab Ghazy.;Florian Müller.;Robin Benedikt Rolnik.;Marcell Lederer.;Ali Hmedat.;Martina Vetter.;Markus Wallwiener.;Wolfgang Sippl.;Stefan Hüttelmaier.;Nadine Bley.
来源: NAR Cancer. 2025年7卷1期zcaf006页
The Hippo/YAP1 signaling pathway regulates normal development by controlling contact inhibition of growth. In cancer, YAP1 activation is often dysregulated, leading to excessive tumor growth and metastasis. SRC kinase can cross talk to Hippo signaling by disrupting adherens junctions, repressing the Hippo cascade, or activating YAP1 to promote proliferation. Here, we demonstrate that the IGF2 messenger RNA-binding protein 1 (IGF2BP1) impedes the repression of YAP1 by Hippo signaling in carcinomas. IGF2BP1 stabilizes the YAP1 messenger RNA (mRNA) and enhances YAP1 protein synthesis through an m6A-dependent interaction with the 3' untranslated region of the YAP1 mRNA, thereby increasing YAP1/TAZ-driven transcription to bypass contact inhibition of tumor cell growth. Inhibiting IGF2BP1-mRNA binding using BTYNB reduces YAP1 levels and transcriptional activity, leading to significant growth inhibition in carcinoma cells and ovarian cancer organoids. In contrast, SRC inhibition with Saracatinib fails to inhibit YAP1/TAZ-driven transcription and cell growth in general. This is particularly significant in de-differentiated, rather mesenchymal carcinoma-derived cells, which exhibit high IGF2BP1 and YAP1 expression, rendering them less reliant on SRC-directed growth stimulation. In such invasive carcinoma models, the combined inhibition of SRC, IGF2BP1, and YAP1/TAZ proved superior over monotherapies. These findings highlight the therapeutic potential of targeting IGF2BP1, a key regulator of oncogenic transcription networks.
650. Dicoumarol sensitizes hepatocellular carcinoma cells to ferroptosis induced by imidazole ketone erastin.
作者: Ziwei Yang.;Tixin Han.;Ruibin Yang.;Yinuo Zhang.;Yifei Qin.;Jialu Hou.;Fei Huo.;Zhuan Feng.;Yaxin Ding.;Jiali Yang.;Gang Zhou.;Shijie Wang.;Xiaohang Xie.;Peng Lin.;Zhi-Nan Chen.;Jiao Wu.
来源: Front Immunol. 2025年16卷1531874页
Ferroptosis, an iron-dependent form of regulated cell death, is characterized by the lethal accumulation of lipid peroxides on cellular membranes. It not only inhibits tumor growth but also enhances immunotherapy responses and overcomes drug resistance in cancer therapy. The inhibition of the cystine-glutamate antiporter, system Xc-, induces ferroptosis. Imidazole ketone erastin (IKE), an inhibitor of the system Xc- functional subunit solute carrier family 7 member 11 (SLC7A11), is an effective and metabolically stable inducer of ferroptosis with potential in vivo applications. However, tumor cells exhibited differential sensitivity to IKE-induced ferroptosis. The intrinsic factors determining sensitivity to IKE-induced ferroptosis remain to be explored to improve its efficacy.
651. The Anti-Aging Mechanism of Metformin: From Molecular Insights to Clinical Applications.
作者: Ting Zhang.;Lijun Zhou.;Meagan J Makarczyk.;Peng Feng.;Jianying Zhang.
来源: Molecules. 2025年30卷4期
Aging represents a complex biological phenomenon marked by the progressive deterioration of physiological functions over time, reduced resilience, and increased vulnerability to age-related diseases, ultimately culminating in mortality. Recent research has uncovered diverse molecular mechanisms through which metformin extends its benefits beyond glycemic control, presenting it as a promising intervention against aging. This review delves into the anti-aging properties of metformin, highlighting its role in mitochondrial energy modulation, activation of the AMPK-mTOR signaling pathway, stimulation of autophagy, and mitigation of inflammation linked to cellular aging. Furthermore, we discuss its influence on epigenetic modifications that underpin genomic stability and cellular homeostasis. Metformin's potential in addressing age-associated disorders including metabolic, cardiovascular, and neurodegenerative diseases is also explored. The Targeting Aging with Metformin (TAME) trial aims to provide key evidence on its efficacy in delaying aging in humans. Despite these promising insights, significant challenges persist in gaining a more comprehensive understanding into its underlying mechanisms, determining optimal dosing strategies, and evaluating long-term safety in non-diabetic populations. Addressing these challenges is crucial to fully realizing metformin's potential as an anti-aging therapeutic.
652. Polyphenol-Based Prevention and Treatment of Cancer Through Epigenetic and Combinatorial Mechanisms.
Polyphenols have been shown to be utilized as an effective treatment for cancer by acting as a DNMT or HDAC inhibitor, reducing inflammatory processes, and causing cell cycle arrest. While there have been many studies demonstrating the anti-cancerous potential of individual polyphenols, there are limited studies on the combinatorial effects of polyphenols. This review focuses on how combinations of different polyphenols can be used as a chemotherapeutic treatment option for patients. Specifically, we examine the combinatorial effects of three commonly used polyphenols: curcumin, resveratrol, and epigallocatechin gallate. These combinations have been shown to induce apoptosis, prevent colony formation and migration, increase tumor suppression, reduce cell viability and angiogenesis, and create several epigenetic modifications. In addition, these anti-cancerous effects were synergistic and additive. Thus, these findings suggest that using different combinations of polyphenols at the appropriate concentrations can be used as a better and more efficacious treatment against cancer as compared to using polyphenols individually.
653. miRNA Signatures as Predictors of Therapy Response in Castration-Resistant Prostate Cancer: Insights from Clinical Liquid Biopsies and 3D Culture Models.
作者: Jonathan Puente-Rivera.;Stephanie I Nuñez-Olvera.;Verónica Fernández-Sánchez.;Monica Alethia Cureño-Díaz.;Erika Gómez-Zamora.;Estibeyesbo Said Plascencia-Nieto.;Elisa Elvira Figueroa-Angulo.;María Elizbeth Alvarez-Sánchez.
来源: Genes (Basel). 2025年16卷2期
Prostate cancer (PCa) patients who do not respond to androgen deprivation therapy (ADT), referred to as castration-resistant prostate cancer (CRPC), remain a clinical challenge due to confirm the aggressive nature of CRPC and its resistance to conventional therapies. This study aims to investigate the potential of microRNAs (miRNAs) as biomarkers for predicting therapeutic response in CRPC patients.
654. Long Noncoding RNAs Responding to Ethanol Stress in Yeast Seem Associated with Protein Synthesis and Membrane Integrity.
作者: Amanda Piveta Schnepper.;Agatha M S Kubo.;Camila Moreira Pinto.;Ramon Hernany Martins Gomes.;Matheus Naia Fioretto.;Luís Antonio Justulin.;Aline M M Braz.;Marjorie de Assis Golim.;Rejane M T Grotto.;Guilherme Targino Valente.
来源: Genes (Basel). 2025年16卷2期
Background/Objectives: Translation and the formation of membraneless organelles are linked mechanisms to promote cell stress surveillance. LncRNAs responsive to ethanol stress transcr_9136 of the SEY6210 strain and transcr_10027 of the BY4742 strain appear to act on tolerance to ethanol in these strains. Here, we investigate whether the ethanol responsiveness of transcr_9136 and transcr_10027 and their role in ethanol stress are associated with protein biogenesis and membraneless organelle assembly. Methods: SEY6210 transcr_9136∆ and BY4742 transcr_10027∆ and their wild-type counterparts were subjected to their maximum ethanol-tolerant stress. The expression of the transcr_9136, transcr_10027, ILT1, RRP1, 27S, 25S, TIR3, and FAA3 genes was accessed by qPCR. The level of DCP1a, PABP, and eIF4E proteins was evaluated by Western blotting. Bioinformatics analyses allowed us to check whether transcr_9136 may regulate the expression of RRP1 and predict the interaction between transcr_10027 and Tel1p. The cell death rate of SEY6210 strains under control and ethanol stress conditions was assessed by flow cytometry. Finally, we evaluated the total protein yield of all strains analyzed. Results: The results demonstrated that transcr_9136 of SEY6210 seems to control the expression of RRP1 and 27S rRNA and reduce the general translation. Furthermore, transcr_9136 seems to act on cell membrane integrity. Transcr_10027 of BY4742 appears to inhibit processing body formation and induce a general translation level. Conclusions: This is the first report on the effect of lncRNAs on yeast protein synthesis and new mechanisms of stress-responsive lncRNAs in yeast, with potential industrial applications such as ethanol production.
655. Impact of UV-Irradiated Mesoporous Titania Nanoparticles (mTiNPs) on Key Onco- and Tumor Suppressor microRNAs of PC3 Prostate Cancer Cells.
作者: Andrea Méndez-García.;Luis Alberto Bravo-Vázquez.;Padmavati Sahare.;Sujay Paul.
来源: Genes (Basel). 2025年16卷2期
Mesoporous titanium dioxide nanoparticles (mTiNPs) are known for their chemical stability, non-toxicity, antimicrobial and anticancer effects, as well as for their photocatalytic properties. When this material is subjected to UV radiation, its electronic structure shifts, and during that process, reactive oxygen species are generated, which in turn exert apoptotic events on the cancer cells.
656. The Antidepressant Sertraline Modulates Gene Expression and Alternative Splicing Events in the Dermatophyte Trichophyton rubrum: A Comprehensive Analysis.
作者: Carlos H Lopes Rocha.;Flaviane M Galvão Rocha.;Pablo R Sanches.;Antonio Rossi.;Nilce M Martinez-Rossi.
来源: Genes (Basel). 2025年16卷2期
Dermatophytosis, a prevalent fungal infection of keratinized tissues, is primarily caused by the filamentous fungus Trichophyton rubrum. Sertraline (SRT), an antidepressant with antifungal activity, has already demonstrated therapeutic potential against this fungus. Elucidating the effects of SRT may provide insights into its mechanism of action and fungal adaptation to this drug. Differential gene expression and alternative splicing (AS) facilitate fungal adaptations to various environmental conditions. This study aimed to provide a comprehensive overview of AS events and their implications in T. rubrum cultivated under sub-inhibitory concentrations of SRT.
657. Combined Effect of Conventional Chemotherapy with Epigenetic Modulators on Glioblastoma.
作者: Adrian Albulescu.;Anca Botezatu.;Alina Fudulu.;Camelia Mia Hotnog.;Marinela Bostan.;Mirela Mihăilă.;Iulia Virginia Iancu.;Adriana Plesa.;Lorelei Brasoveanu.
来源: Genes (Basel). 2025年16卷2期
Glioblastoma is the most common malignant primary brain tumor, characterized by necrosis, uncontrolled proliferation, infiltration, angiogenesis, apoptosis resistance, and genomic instability. Epigenetic modifiers hold promise as adjuvant therapies for gliomas, with synergistic combinations being explored to enhance efficacy and reduce toxicity. This study aimed to evaluate the effects of single or combined treatments with various anticancer drugs (Carboplatin, Paclitaxel, Avastin), natural compounds (Quercetin), and epigenetic modulators (suberoylanilide hydroxamic acid and 5-Azacytidine) on the expression of some long noncoding RNAs and methylation drivers or some functional features in the U87-MG cell line.
658. Targeting Heat Shock Transcription Factor 4 Enhances the Efficacy of Cabozantinib and Immune Checkpoint Inhibitors in Renal Cell Carcinoma.
作者: Saeki Saito.;Hirofumi Yoshino.;Seiya Yokoyama.;Mitsuhiko Tominaga.;Gang Li.;Junya Arima.;Ichiro Kawahara.;Ikumi Fukuda.;Akihiko Mitsuke.;Takashi Sakaguchi.;Satoru Inoguchi.;Ryosuke Matsushita.;Yasutoshi Yamada.;Shuichi Tatarano.;Akihide Tanimoto.;Hideki Enokida.
来源: Int J Mol Sci. 2025年26卷4期
Recently, immune checkpoint inhibitors (ICIs) and cabozantinib, a tyrosine kinase inhibitor (TKI), have been used to treat renal cell carcinoma (RCC); the combination of these agents has become a standard treatment for RCC. TKIs generally target vascular endothelial growth factor. However, cabozantinib is characterized by its targeting of MET. Therefore, cabozantinib can be used as a late-line therapy for TKI-resistant RCC. According to data from The Cancer Genome Atlas (TCGA), heat shock transcription factor 4 (HSF4) expression is higher in RCC tissues than in normal renal tissues. HSF4 binds to the MET promoter in colorectal carcinoma to enhance MET expression and promote tumor progression. However, the functional role of HSF4 in RCC is unclear. We performed loss-of-function assays of HSF4, and our results showed that HSF4 knockdown in RCC cells significantly decreased cell functions. Moreover, MET expression was decreased in HSF4-knockdown cells but elevated in sunitinib-resistant RCC cells. The combination of cabozantinib and HSF4 knockdown reduced cell proliferation in sunitinib-resistant cells more than each monotherapy alone. Furthermore, HSF4 knockdown combined with an ICI showed synergistic suppression of tumor growth in vivo. Overall, our strategy involving HSF4 knockdown may enhance the efficacy of existing therapies, such as cabozantinib and ICIs.
659. miR-212-5p Regulates PM2.5-Induced Apoptosis by Targeting LAMC2 and LAMA3.
作者: Yunna Jia.;Xiqing Zhang.;Cuizhu Zhao.;Zhenhua Ma.;Ke Sun.;Yize Sun.;Xiaohui Du.;Meng Liu.;Xiaojun Liang.;Xiuzhen Yu.;Yunhang Gao.
来源: Int J Mol Sci. 2025年26卷4期
Fine particulate matter (PM2.5) is often linked to a range of respiratory diseases and cellular damage. Although studies have shown that the expression profiles of microRNAs (miRNAs) are altered during lung damage brought on by PM2.5, the underlying functions of miRNAs remain poorly understood. In this research, we explored the role of PM2.5-induced apoptosis in detail and focused on the miRNA (miR-212-5p) that regulates apoptosis. Through a dual-luciferase assay, a direct targeting connection between laminin subunits γ2 (LAMC2) and α3 (LAMA3) and miR-212-5p was successfully demonstrated. This study focused on revealing the negative regulatory relationship between miR-212-5p and LAMC2 and LAMA3, providing important clues for a deeper understanding of the relevant physiological and pathological mechanisms. The present study showed that LAMC2 and LAMA3 positively regulate the PI3K-AKT pathway and negatively regulate the NF-κB pathway, which directly leads to significant changes in apoptosis rates. This study reveals a previously unrecognized molecular mechanism by showing that miR-212-5p directly targets LAMC2 and LAMA3 and thus associates with PM2.5-induced apoptosis via the PI3K/AKT/NF-κB pathway. These findings not only redefine the role of miR-212-5p in apoptosis but also open up new avenues for future research.
660. ANKRD2 Knockdown as a Therapeutic Strategy in Osteosarcoma: Effects on Proliferation and Drug Response in U2OS and HOS Cells.
作者: Vittoria Cenni.;Alberto Bavelloni.;Cristina Capanni.;Elisabetta Mattioli.;Federico Bortolozzo.;Snezana Kojic.;Giulia Orlandi.;Jessika Bertacchini.;William L Blalock.
来源: Int J Mol Sci. 2025年26卷4期
Ankrd2, a mechanoresponsive protein primarily studied in muscle physiology, is emerging as a player in cancer progression. This study investigates the functional role of Ankrd2 in osteosarcoma cells, revealing its critical involvement in cell proliferation and response to chemotherapeutic drugs. We showed that Ankrd2 knockdown impairs the activation of PI3K/Akt and ERK1/2 pathways, reduces levels of cell cycle regulators including cyclin D1 and cyclin B, and counteracts the expression of nuclear lamin A and lamin B, disrupting nuclear morphology and DNA integrity. Strikingly, the loss of Ankrd2 enhances the sensitivity of osteosarcoma cells to doxorubicin and cisplatin, highlighting Ankrd2 potential as a therapeutic target to improve chemotherapeutic efficacy. Defining a novel mechanistic role for Ankrd2 in promoting tumor progression, we propose that Ankrd2 reduction could be exploited as an adjuvant strategy to enhance the efficacy of chemotherapy, offering new therapeutic opportunities for OS treatment.
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