Molecular medicine reports最新文献

{"title":"Reduced iron bioavailability drives acute high‑altitude lung injury through HIF1α activation and mitophagy.","authors":"Yumei Geng, Yu Hu, Huijie Wang, Fang Zhang, Ri-Li Ge","doi":"10.3892/mmr.2025.13580","DOIUrl":"10.3892/mmr.2025.13580","url":null,"abstract":"<p><p>High‑altitude pulmonary injury, characterized by pulmonary edema and pulmonary hypertension, is mechanistically driven by dysregulated mitophagy, as evidenced by impaired mitochondrial quality control in endothelial cells under hypobaric hypoxia. Iron supplementation for individuals who have ascended rapidly to high altitudes can effectively mitigate the phenomenon of hypoxic pulmonary vasoconstriction; however, the precise role and detailed mechanisms remain to be determined. The present study aimed to explore the role and mechanism of iron in acute hypoxia‑induced lung injury. Sprague‑Dawley rats were initially placed in a hypobaric hypoxia chamber for various durations to determine the optimal time for acute hypoxia‑induced lung injury. The rats were exposed to a hypobaric hypoxia chamber for 3 days, during which they were treated with an iron chelator or iron sucrose. Mean pulmonary artery pressure (mPAP) was measured to assess hypoxic pulmonary vascular response. Furthermore, the degree of lung injury was assessed by calculating the pulmonary wet/dry weight ratio, and via morphological evaluation of lung tissues and the pulmonary vasculature. Immunofluorescence and western blot analysis were performed to assess hypoxia‑inducible factor 1α (HIF1α) expression and mitophagy levels. Edu and Cell Counting Kit 8 assays were conducted to evaluate cell proliferation under acute hypoxia. In addition, immunofluorescence and western blot analysis were performed to evaluate the expression levels of proteins associated with cell apoptosis and mitophagy. The results indicated that mitophagy (LC3B‑II/LC3B‑I expression), pulmonary edema (lung wet/dry weight ratio) and lung injury score were most significant after 3 days of hypoxia. However, mitophagy (LC3B‑II/LC3B‑I ratio) and lung injury scores peaked after 4 weeks of hypoxic conditions. Furthermore, an iron chelator was observed to promote pulmonary edema, elevate mPAP and cause lung injury. Conversely, iron sucrose was shown to attenuate lung injury in acute hypoxia. The mechanistic findings indicated that acute hypoxia induced HIF1α activation and increased mitophagy, which promoted a reduction in proliferation and an increase in the apoptosis of pulmonary artery endothelial cells. Furthermore, the iron chelator promoted, whereas iron sucrose ameliorated, the abnormal alterations in pulmonary artery endothelial cells under acute hypoxia. In conclusion, the present study demonstrated that a reduction in iron bioavailability in acute hypoxia may promote HIF1α activation and increased mitophagy, which in turn has been linked to the development of pulmonary edema, elevated mPAP and lung injury. The administration of iron supplementation may be considered an effective method for the alleviation of the aforementioned abnormalities resulting from acute hypoxia.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Splice‑site variant c.3531+1G>T in <i>COL1A1</i> in a family with osteogenesis imperfecta.","authors":"Yanru Huang, Yixi Zhou, Lutan Zhang, Ye Shen, Xingmei Yao, Jieqiong Xie, Libin Mei, Yunsheng Ge","doi":"10.3892/mmr.2025.13582","DOIUrl":"10.3892/mmr.2025.13582","url":null,"abstract":"<p><p>Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by high genetic and phenotypic heterogeneity. Notably, 90% of cases of OI are caused by pathogenic variants in the <i>COL1A1</i> and <i>COL1A2</i> genes, with those in <i>COL1A1</i> being the most common. The present study aimed to investigate the genetic etiology of OI in a family and the pathogenicity of the splice‑site variant. Whole‑exome sequencing was performed for the proband and Sanger sequencing was performed for all family members to validate the results. Reverse transcription (RT)‑PCR on lymphocyte strains was performed on the proband and an age‑matched control, and minigene experiments were performed to verify the splicing patterns. A heterozygous variant, c.3531+1G>T, was detected in <i>COL1A1</i> in all patients in the family. RT‑PCR showed an increase in abnormal transcript expression and a decrease in normal transcript expression in the proband. Minigene splicing assays revealed that the mutant gene exhibited four splicing patterns, whereas the normal gene exhibited three splicing patterns. This finding indicated that the c.3531+1G>T variant site affected intron 47 splicing. To the best of our knowledge, this variant was first reported in the Palestinian population, whereas the present study is the first to report this variant in the Chinese population and to clarify the effect of this variant. The results expand the spectrum of pathogenic variants associated with OI.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Retracted] Effect of selective inhibition or activation of PGE2 EP1 receptor on glomerulosclerosis.","authors":"Xu Chen, Jun Yin, Yuyin Xu, Zhi Qiu, Jing Liu, Xiaolan Chen","doi":"10.3892/mmr.2025.13538","DOIUrl":"https://doi.org/10.3892/mmr.2025.13538","url":null,"abstract":"<p><p>Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the immunohistochemical images shown in Fig. 2C and 3A, at least four pairs of data panels showed evidence of overlapping data, both within the same figure parts and comparing between them. Owing to the large number of data duplication events that have been identified in this paper, the Editor of <i>Molecular Medicine Reports</i> has decided that it should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 22: 2887‑2895, 2020; DOI: 10.3892/mmr.2020.11353].</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co‑treatment with triptolide and RSL3 induces hepatocellular carcinoma cell apoptosis and ferroptosis.","authors":"Weixia Liu, Guodi Wu, Jing Wang, Shanshan Wu, Zhi Chen","doi":"10.3892/mmr.2025.13567","DOIUrl":"10.3892/mmr.2025.13567","url":null,"abstract":"<p><p>Glutathione peroxidase 4 (GPx4; also known as phospholipid hydroperoxide glutathione peroxidase) inhibits cell death, including apoptosis and ferroptosis, by reducing lipid peroxidation. In addition, western blot assays showed that GPx4 protein levels were elevated in hepatocellular carcinoma (HCC) cells following triptolide (TPL) treatment. Therefore, it was hypothesized that HCC cells might develop partial resistance to TPL‑induced cytotoxicity through upregulation of the GPx4 protein. To enhance anti‑proliferative efficacy, the present study co‑treated HCC cells with a combination of TPL and RAS‑selective lethal 3 (RSL3), a well‑characterized GPx4 activity inhibitor. Subsequent experimental data produced from Cell Counting Kit‑8 and flow cytometric analyses demonstrated that co‑administration of TPL and RSL3 promoted HCC cell apoptosis, elevated intracellular reactive oxygen species levels and induced ferroptosis. These collective findings suggested that co‑treatment with TPL and RSL3 may induce both apoptotic and ferroptotic pathways in HCC cells.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eburicoic acid inhibits endothelial cell pyroptosis and retards the development of atherosclerosis through the Keap1/Nrf2/HO‑1/ROS pathway.","authors":"Meng-Qing Ma, Chun Yang, Shi-Yu Jin, Yu Yang, Yan-Yan Pan, Xian-He Lin","doi":"10.3892/mmr.2025.13551","DOIUrl":"10.3892/mmr.2025.13551","url":null,"abstract":"<p><p>Atherosclerosis (AS)‑related coronary artery disease is the main cause of morbidity and mortality around the globe. Eburicoic acid, a triterpenoid compound from <i>Antrodia camphorata</i>, exerts anti‑inflammatory and anti‑hyperlipidemic effects, although its role in atherogenesis remains unknown. Endothelial cell pyroptosis‑caused chronic inflammatory response within vessel walls is a critical initial event in atherogenesis, making it a promising target to prevent AS. The present study was designed to investigate the effects of eburicoic acid on endothelial cell pyroptosis, AS progression and the underlying mechanisms. The results showed that with dose and time increased, treatment of human umbilical vascular endothelial cells (HUVECs) with eburicoic acid markedly decreased the expression of Kelch‑like ECH‑associated protein 1 (Keap1), NF‑E2‑related factor 2 (Nrf2), reactive oxygen species (ROS), NLR family pyrin domain‑containing protein 3 (NLRP3), cleaved caspase‑1, apoptosis‑associated speck‑like protein containing CARD (ASC), N‑terminal gasdermin‑D (GSDMD‑N), downregulated the secretion levels of pro‑inflammatory cytokines interleukin (IL) 1β, IL‑6 and IL‑18, inhibited caspase‑1 activity and lactate dehydrogenase release and improved plasma membrane integrity. By contrast, the expression of nuclear Nrf2, total Nrf2 and heme oxygenase‑1 (HO‑1) were increased by eburicoic acid treatment in HUVECs dose‑ and time‑dependently. Moreover, the inhibitory effects of eburicoic acid on HUVEC pyroptosis were mainly compromised by pre‑treatment with ROS agonist, HO‑1 small interfering (si)RNA, or Nrf2 siRNA. Finally, it was observed that administering high‑fat‑diet fed ApoE‑/‑ mice with eburicoic acid markedly increased Nrf2 and HO‑1 levels and reduced the expression of Keap1, NLRP3, cleaved caspase‑1, ASC and GSDMD‑N in aortas and ameliorated hyperlipidemia and inflammation in the serum, leading to smaller atherosclerotic plaques, less lipid accumulation and high content of collagen fiber within plaques. These findings identified eburicoic acid as a potent anti‑atherogenic natural product by suppressing endothelial cell pyroptosis via the Keap1/Nrf2/HO‑1/ROS pathway. Eburicoic acid may be considered an effective phytomedicine for treating AS.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer effects of salvianolic acid A through multiple signaling pathways (Review).","authors":"Cheng-Xia Li, Qi Xu, Shi-Ting Jiang, Dan Liu, Chao Tang, Wen-Li Yang","doi":"10.3892/mmr.2025.13541","DOIUrl":"10.3892/mmr.2025.13541","url":null,"abstract":"<p><p><i>Salvia miltiorrhiza</i> Bunge (<i>Salvia miltiorrhiza</i>), commonly referred to as Danshen, is a well‑known herb in traditional Chinese medicine, the active ingredients of which are mostly categorized as water soluble and lipid soluble. Salvianolic acids are the major water‑soluble phenolic acid constituents of Danshen; salvianolic acid B is the most prevalent, with salvianolic acid A (SAA) being the next most predominant form. SAA offers a wide array of pharmacological benefits, including cardiovascular protection, and anti‑inflammatory, antioxidant, antiviral and anticancer activities. SAA is currently undergoing phase III clinical trials for diabetic peripheral neuropathy and has shown protective benefits against cardiovascular illnesses; furthermore, its safety and effectiveness are encouraging. By targeting several signaling pathways, preventing cell cycle progression, tumor cell migration, invasion and metastasis, normalizing the tumor vasculature and encouraging cell apoptosis, SAA can also prevent the growth of malignancies. In addition, it enhances sensitivity to chemotherapeutic drugs, and alleviates their toxicity and side effects. However, the broad therapeutic use of SAA has been somewhat limited by its low content in <i>Salvia miltiorrhiza</i> Bunge and the difficulty of its extraction techniques. Therefore, the present review focuses on the potential mechanisms of SAA in tumor prevention and treatment. With the anticipation that SAA will serve a notable role in clinical applications in the future, these discoveries may offer a scientific basis for the combination of SAA with conventional chemotherapeutic drugs in the treatment of cancer, and could establish a foundation for the development of SAA as an anticancer drug.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indolepropionic acid modulates the immune response in allergic rhinitis through the AKT/CEBPB/IL‑10 signaling pathway.","authors":"Lu Gao, Yulan Song, Fengyao Zhang, Yan Zhao, Huixuan Hu, Yan Feng","doi":"10.3892/mmr.2025.13569","DOIUrl":"10.3892/mmr.2025.13569","url":null,"abstract":"<p><p>Allergic rhinitis (AR) is a common inflammatory disorder of the nasal mucosa, usually triggered by environmental allergens. Indolepropionic acid (IPA) can influence immune responses; however, the specific mechanisms underlying the effects of IPA on immune regulation in AR remain largely unexplored. In the present study, an experimental mouse model of AR was established by sensitizing and exposing the mice to allergens, followed by the administration of IPA via gavage. Nasal symptoms were assessed through behavioral scoring, histological examinations were conducted to evaluate changes in nasal mucosa, and cytokine levels were quantified using ELISA. The expression of key signaling molecules was analyzed by immunohistochemistry, reverse transcription‑quantitative PCR and western blotting. Additionally, the effects of IPA combined with an AKT inhibitor (HY‑10355) on signaling pathway‑related proteins in human nasal epithelial cells were evaluated using cellular immunofluorescence and western blotting. The results revealed that IPA treatment significantly reduced nasal inflammation, as indicated by decreased sneezing and mucus secretion. Histological analysis showed reduced inflammatory cell infiltration and epithelial damage in IPA‑treated mice compared to controls. Furthermore, cytokine analysis revealed reduced levels of the pro‑inflammatory cytokines IL‑4, IL‑5, IL‑13 and immunoglobulin E, along with increased levels of the anti‑inflammatory cytokine IL‑10. Molecular investigations demonstrated that IPA can activate the AKT/CCAAT enhancer binding protein β pathway, leading to increased IL‑10 expression and reduced inflammation. In conclusion, these findings suggested that IPA may serve as a promising therapeutic strategy for managing AR, pending further clinical validation.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic profiling of autophagy and apoptosis pathways in liver cancer cells treated with a new tyrosine kinase inhibitor PD161570.","authors":"Xingxing He, Jianping Liu, Yulian Zhang, Bushan Xie","doi":"10.3892/mmr.2025.13540","DOIUrl":"https://doi.org/10.3892/mmr.2025.13540","url":null,"abstract":"<p><p>Liver cancer is the third most lethal and prevalent cancer in the Asia‑Pacific regions. Despite the use of tyrosine kinase inhibitors as first‑ and second‑line therapies, the overall survival rate for advanced liver cancer remains dismal and has not improved over the past decade. The present study, through high‑throughput screening, identified and demonstrated that PD161570, a new tyrosine kinase inhibitor, inhibited cell growth and proliferation in liver cancer cells. Mechanistically, PD161570 induced autophagy and enhanced autophagic flux in an autophagy‑related gene (ATG5)‑dependent and mammalian target of rapamycin kinase‑independent manner. Furthermore, when combined with chloroquine treatment, PD161570 not only suppressed cell proliferation but also increased cell apoptosis due to autophagy inhibition. RNA sequencing analysis revealed 1,121 differentially expressed genes in liver cancer cells following PD161570 treatment under autophagy inhibition via ATG5 knockdown. Notably, key molecules involved in autophagy (such as Damage Regulated Autophagy Modulator 1) and apoptosis regulators (including HRK, CTSS, BIRC3, BBC3, DDIT3 and GADD45B), were identified. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), demonstrated enrichment in apoptotic and cell death signaling pathways, highlighting the critical role of the mitogen‑activated protein kinases signaling pathway. In conclusion, PD161570 elicited an ATG5‑dependent autophagic process in liver cancer cells, while simultaneously enhancing apoptosis under conditions of autophagy inhibition.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sevoflurane: A dual modulator of miR‑211‑5p and mitochondrial apoptosis in glioma therapy.","authors":"Haili Wang, Guofang Cheng, Shuyuan Zhang, Haibo Qu, Xibo Zhao, Ailing Yang, Xuejia Sun, Hua Pan","doi":"10.3892/mmr.2025.13544","DOIUrl":"https://doi.org/10.3892/mmr.2025.13544","url":null,"abstract":"<p><p>The present study aimed to investigate how sevoflurane (SEV) regulated the apoptosis of glioma cells through the mitochondrial apoptosis pathway. First, an evaluation was performed on the viability, apoptosis, mitochondrial reactive oxygen species levels, mitochondrial membrane potential and apoptosis and autophagy‑related protein expression of glioma cells according to experimental groups. Next, the expression of microRNA‑211‑5p (miR‑211‑5p), silent information regulator 1 (SIRT1) and phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (AKT) signaling pathway was detected by reverse transcription‑quantitative PCR or western blotting. Dual luciferase reporter gene assay confirmed the targeting relationship between miR‑211‑5p and SIRT1. In addition, SEV suppressed the proliferation and induced the apoptosis in human glioma cell line cells via the mitochondrial apoptosis pathway. In mechanistic analysis, the miR‑211‑5p level in glioma cells was low, while following SEV treatment, it was increased. Furthermore, SEV regulated SIRT1 by upregulating miR‑211‑5p expression, thereby blocking the PI3K/AKT signaling pathway activation. Moreover, functional rescue experiments showed that downregulation of SIRT1 or miR‑211‑5p could reverse the effects of SEV on glioma cells. Collectively, SEV promoted apoptosis in glioma cells by inducing miR‑211‑5p, which regulated SIRT1/PI3K/AKT pathway, mediating mitochondria‑dependent apoptosis pathway. This finding may open new possibilities for SEV as a potential treatment for glioma in the future.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of Bcl‑2 in controlling the transition between autophagy and apoptosis (Review).","authors":"Ahmet Alperen Palabiyik","doi":"10.3892/mmr.2025.13537","DOIUrl":"10.3892/mmr.2025.13537","url":null,"abstract":"<p><p>The Bcl‑2 protein family serves a key role in maintaining cellular homeostasis by regulating the balance between autophagy and apoptosis. The present review aimed to summarize interactions of Bcl‑2 with key proteins, including Beclin 1, Bax and Bcl‑2 homologous antagonist/killer, as well as its influence on cellular processes such as mitophagy, nutrient sensing and endoplasmic reticulum stress response. The impact of post‑translational modifications of Bcl‑2, including phosphorylation, ubiquitination and sumoylation, is discussed with respect to their regulatory roles under stress. In pathological states, Bcl‑2 upregulation in cancer suppresses apoptosis and autophagy, thereby facilitating tumor survival and resistance to chemotherapy. Conversely, in neurodegenerative diseases, impaired autophagy and increased apoptosis contribute to neuronal loss. Therapeutic strategies targeting Bcl‑2 (for example inhibitors such as venetoclax, navitoclax, obatoclax and combination therapies involving autophagy modulators) were evaluated for their potential efficacy. There is lack of understanding of tissue‑specific functions of Bcl‑2 and its interactions with non‑coding RNAs. Future research should prioritize these areas and leverage advanced single‑cell technologies to elucidate the real‑time dynamics of Bcl‑2 in cell processes. The present review highlights the key role of Bcl‑2 in cell fate determination and highlights its potential as a therapeutic target, offering insight for the development of innovative treatments for cancer, neurodegenerative disorder and age‑related diseases.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}