Biochimica et biophysica acta. Molecular basis of disease最新文献

{"title":"Keloid vasculature reacts to intralesional injection therapies but does not predict the response to treatment: Biopsies from double-blinded, randomized, controlled trial","authors":"Tuomas Komulainen ,&nbsp;Kristiina E. Hietanen ,&nbsp;Teemu Tolonen ,&nbsp;Seppo Parkkila ,&nbsp;Ilkka S. Kaartinen ,&nbsp;Tero A.H. Järvinen","doi":"10.1016/j.bbadis.2025.167790","DOIUrl":"10.1016/j.bbadis.2025.167790","url":null,"abstract":"<div><div>Keloids are benign fibroproliferative skin scars that expand beyond the original wound site. Hypoxia and angiogenesis are thought to drive pathological scar formation in keloids. We utilized biopsies collected before, during and after the double-blinded randomized controlled trial (RCT) comparing the intralesional treatments of 5-fluorouracil and triamcinolone injections in 48 human keloids. We could not detect any cells expressing the hypoxia markers (carbonic anhydrase 9 and hypoxia-inducible factor 1α) in the three distinct regions of keloid dermis. The amount of epidermal hypoxia could not predict the response to treatment. The middle dermis of the patients obtaining a clinical response to the intralesional injections showed significant increase in mature blood vessels and in lymphatics after the treatment. Our study does not support hypoxia being the driver behind keloid formation but demonstrates that the patients obtaining a response to intralesional therapies develop more blood vessels and lymphatics in the middle dermis of the keloids during the treatment.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167790"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628419","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":"Activation, interaction and intimation of Nrf2 pathway and their mutational studies causing Nrf2 associated cancer","authors":"Mridul Sahu,&nbsp;Utkarsh Jain","doi":"10.1016/j.bbadis.2025.167764","DOIUrl":"10.1016/j.bbadis.2025.167764","url":null,"abstract":"<div><div>Responses against infection trigger several signaling pathways that lead to the production of cytokines, these cytokines release ROS and RNS, damaging DNA and proteins turn into various diseases including cancer. To combat these harmful cytokines, the Nrf2 pathway is activated. The gene NFE2L2 encodes Nrf2, which is divided into seven conserved domains (Neh1–7). The DLG and ETGE motifs, conserved sequences of amino acid in the Neh2 domain of Nrf2, bind to the BTB domain of Keap1. BTB domain promotes Keap1's homodimerization resulting in Cul3 recruitment providing scaffold formation to E2 ubiquitin ligase to form ubiquitin complex. Under normal conditions, this complex regularly degrades Nrf2. However, once the cell is exposed to oxidative stress by ROS interaction with Keap1 resulting in conformational changes that stabilize the Nrf2. Nrf2 further concentrates on the nucleus where it binds with the transcriptional factor to perform the desired genes transcription for synthesizing SOD, GSH, CAT, and various other proteins which reduce the ROS levels preventing certain diseases. To prevent cells from oxidative stress, molecular hydrogen activates the Nrf2 pathway. To activate the Nrf2 pathway, molecular hydrogen oxidizes the iron porphyrin which acts as an electrophile and interacts with Keap1's cysteine residue.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167764"},"PeriodicalIF":4.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619633","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":"N6-methyladenosine RNA modification in stomach carcinoma: Novel insights into mechanisms and implications for diagnosis and treatment","authors":"Zhengmao Lu ,&nbsp;Zhaojie Lyu ,&nbsp;Peixin Dong ,&nbsp;Yunmei Liu ,&nbsp;Lei Huang","doi":"10.1016/j.bbadis.2025.167793","DOIUrl":"10.1016/j.bbadis.2025.167793","url":null,"abstract":"<div><div>N6-methyladenosine (m⁶A) RNA methylation is crucially involved in the genesis and advancement of gastric cancer (GC) by controlling various pathobiological aspects including gene expression, signal transduction, metabolism, cell death, epithelial-mesenchymal transition, angiogenesis, and exosome function. Despite its importance, the exact mechanisms by which m⁶A modification influences GC biology remain inadequately explored. This review consolidates the latest advances in uncovering the mechanisms and diverse roles of m⁶A in GC and proposes new research and translational directions. Key regulators (writers, readers, and erasers) of m⁶A, such as METTL3/14/16 and WTAP, significantly affect cancer progression, anticancer immune response, and treatment outcomes. m⁶A modification also impacts immune cell infiltration and the tumor microenvironment, highlighting its potential as a diagnostic and prognostic marker. Interactions between m⁶A methylation and non-coding RNAs offer further novel insights into GC development and therapeutic targets. Targeting m⁶A regulators could enhance immunotherapy response, overcome treatment resistance, and improve oncological and clinical outcomes. Models based on m⁶A can precisely predict treatment response and prognosis in GC. Additional investigation is needed to fully understand the mechanisms of m⁶A methylation and its potential clinical applications and relevance (e.g., as precise markers for early detection, prediction of outcome, and response to therapy and as therapeutic targets) in GC. Future research should focus on in vivo studies, potential clinical trials, and the examination of m⁶A modification in other types of cancers.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167793"},"PeriodicalIF":4.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619632","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":"NAT2 activity increases cytotoxicity of anthracycline antibiotics and HDAC inhibitors","authors":"Natallia Rameika ,&nbsp;Ioanna Tsiara ,&nbsp;Xiaonan Zhang ,&nbsp;Wawrzyniec Haberek ,&nbsp;Verónica Rendo ,&nbsp;Snehangshu Kundu ,&nbsp;Mario S.P. Correia ,&nbsp;Ivaylo Stoimenov ,&nbsp;Daniel Globisch ,&nbsp;Tobias Sjöblom","doi":"10.1016/j.bbadis.2025.167755","DOIUrl":"10.1016/j.bbadis.2025.167755","url":null,"abstract":"<div><div>The Arylamine-<em>N</em>-acetyltransferase-2 (NAT2) enzyme is involved in metabolism of commonly used drugs driving differences in efficacy and tolerability of treatments. To bridge the current knowledge gap on metabolism of cytotoxic drugs by NAT2, and identify anticancer agents whose effects depend on NAT2 activity, we assessed 147 clinically used drugs. Hit compounds were evaluated for metabolic conversion by acetylation in presence of recombinant NAT2. Among those 147 drugs we found doxorubicin, daunorubicin, epirubicin, valrubicin, teniposide, afatinib, carmustine, vincristine, panobinostat, and vorinostat to have increased toxicity to cancer cells expressing the rapid <em>NAT2</em> allele. Additionally, we report NAT2-mediated acetylation of idarubicin, daunorubicin, doxorubicin, vorinostat, and CUDC-101. These findings have implications for pharmacogenomics and cancer precision medicine using conventional chemotherapeutic drugs, as improving their efficacy and safety may affect &gt;4 million cancer patients worldwide that receive these drugs as standard of care.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167755"},"PeriodicalIF":4.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610868","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":"MBD2 promotes epithelial-to-mesenchymal transition (EMT) and ARDS-related pulmonary fibrosis by modulating FZD2","authors":"Yang Zhou ,&nbsp;Guifang Yang ,&nbsp;Jiqiang Liu ,&nbsp;Shuo Yao ,&nbsp;Jingsi Jia ,&nbsp;Xianming Tang ,&nbsp;Xun Gong ,&nbsp;Fang Wan ,&nbsp;Ren Wu ,&nbsp;Zhenyu Zhao ,&nbsp;Hengxing Liang ,&nbsp;Linxia Liu ,&nbsp;Qimi Liu ,&nbsp;Shanshan Xie ,&nbsp;Xian Long ,&nbsp;Xudong Xiang ,&nbsp;Guyi Wang ,&nbsp;Bing Xiao","doi":"10.1016/j.bbadis.2025.167798","DOIUrl":"10.1016/j.bbadis.2025.167798","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the role and underlying mechanism of Methyl-CpG binding domain protein 2 (MBD2) in the pathogenesis of acute respiratory distress syndrome (ARDS)-related pulmonary fibrosis.</div></div><div><h3>Methods</h3><div>Murine models for ARDS-related pulmonary fibrosis were established in wildtype or MBD2 knockout mice, expressions of MBD2 were determined with immunohistochemistry (IHC), immunofluorescence, and western blot. Epithelial-to-mesenchymal transition (EMT) was detected with determined with decreased expression of E-cadherin and increased expressions of N-cadherin, Vimentin, and α-smooth muscle actin (α-SMA). Transforming growth factor β (TGF-β) treated mouse lung epithelial-12 (MLE-12) cells and primary human type II alveolar epithelial cells were applied to establish in vitro model for EMT. Transcriptional sequencing with RNA-Seq and Chromatin immunoprecipitation (ChIP) assay were used to explore the potential targets of MBD2. Single cell sequencing data and Human pulmonary fibrosis samples were analyzed.</div></div><div><h3>Results</h3><div>Bleomycin (BLM) and lipopolysaccharide (LPS) induced EMT, pulmonary fibrosis, and increased expression of MBD2 in alveolar epithelial cells of mice, and MBD2 knockout significantly alleviated BLM- and LPS-induced pulmonary fibrosis and EMT. TGF-β induced EMT and elevated MBD2 expressions in alveolar epithelial cells, which was mitigated by MBD2 knockdown and aggravated by MBD2 overexpression. Frizzled 2 (FZD2) was found to be the potential target of MBD2. Single-cell sequencing analysis of ARDS patients suggested elevated expression of MBD2 in alveolar epithelial cells, and MBD2 expression was elevated in the lungs of patients with pulmonary fibrosis.</div></div><div><h3>Conclusion</h3><div>Our results indicated that MBD2 could promote EMT and ARDS-related pulmonary fibrosis, potentially by modulating the expression of FZD2.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167798"},"PeriodicalIF":4.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610815","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":"AAV8-mediated silencing of Atad3 prevents the progression from simple steatosis to MASH in mice by reduced IL6 secretion","authors":"Liting Chen ,&nbsp;Yuchang Li ,&nbsp;Rahil Nitinkumar Patel ,&nbsp;Chantal Sottas ,&nbsp;Mahima Chandrakant Raul ,&nbsp;Nrupa Dinesh Patel ,&nbsp;Alexander Zambidis ,&nbsp;Meng Li ,&nbsp;Shefali Chopra ,&nbsp;Vassilios Papadopoulos","doi":"10.1016/j.bbadis.2025.167792","DOIUrl":"10.1016/j.bbadis.2025.167792","url":null,"abstract":"<div><div>ATAD3A deficiency in hepatocytes has been shown to promote simple steatosis (SS). ATAD3 is upregulated in MCD diet-induced MASH. Since the MCD diet is commonly used to induce liver fibrosis, which is related to HSCs activation, we are prompted to investigate the functions of ATAD3 in these two cell types and their mediated transition from SS to MASH. To investigate the role of ATAD3A in HSCs, human LX-2 cells were treated with TGFβ. The results showed that ATAD3A expression was linked to the fibrotic markers ACTA2 and COL1A1. Knockdown of <em>ATAD3A</em> reversed TGFβ-induced HSC activation by downregulating both canonical (SMAD2/3) and non-canonical (ERK1/2 and p38 MAPK) TGFβ signaling pathways. To examine the effect of ATAD3 on the transition from SS to MASH, MASH was induced in mice using the GAN diet for 24 weeks. After 12 weeks, AAV8-conjugated <em>Atad3</em> shRNA was administered to knock down <em>Atad3</em> in the liver. This intervention suppressed steatosis and fibrosis while enhancing insulin sensitivity. Further analysis using conditioned medium (CM) from WT and <em>ATAD3A KO</em> Huh7 cells treated with LPS and PA revealed that IL-6 secretion from Huh7 hepatocytes activated HSCs. However, IL-6 secretion was diminished in <em>ATAD3A KO</em> CM. CM from <em>ATAD3A KO</em> cells also suppressed expression of fibrotic markers ACTA2, P<img>P38, and P-SMAD3 compared to WT cells under MASH conditions. These data suggest that AAV8-mediated <em>Atad3</em> silencing in hepatocytes prevents the transition from SS to MASH, at least in part, by downregulating IL-6 secretion to suppress HSC activation in MASH.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167792"},"PeriodicalIF":4.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610960","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":"CircPICALM promotes neonatal acute kidney injury triggered by hypoxia/reoxygenation via sponging microRNA-204-5p","authors":"Yang Yang ,&nbsp;Jing-jing Pan ,&nbsp;Xiao-qing Chen ,&nbsp;Jia Shi ,&nbsp;Mu-zi Wang ,&nbsp;Tian-yu Liu ,&nbsp;Xiao-guang Zhou","doi":"10.1016/j.bbadis.2025.167795","DOIUrl":"10.1016/j.bbadis.2025.167795","url":null,"abstract":"<div><h3>Background</h3><div>Circular RNAs (circRNAs) have been documented to regulate neonatal acute kidney injury (AKI). Based on previous RNA-sequence findings, circPICALM exhibited significantly disparate expression between AKI newborns and Controls. This study aimed to provide further insights into the regulatory mechanism of circPICALM in neonatal AKI.</div></div><div><h3>Methods</h3><div>C57BL/6 mice born 7 days were divided into Control group and hypoxia groups (11%O₂ and 8%O₂ groups). Human tubule epithelial cells (HK-2) were stimulated with hypoxia/reoxygenation (H/R) to establish an AKI cell model. Through overexpression and knockdown techniques, the regulatory role of circPICALM in H/R-induced kidney injury was explored. Inflammatory cytokines, cell apoptosis, and oxidative stress were also detected to confirm the regulatory function of circPICALM in neonatal AKI.</div></div><div><h3>Results</h3><div>RT-qPCR confirmed that circPICALM was highly expressed in the serum of AKI newborns, neonatal I/R mice and H/R-treated HK-2 cells. Functionally, circPICALM exacerbated H/R-induced HK-2 cell injury by aggravating apoptosis and mitochondrial oxidative stress, increasing the expression of inflammatory factors, including IL-6, IL-1β, and TNF-α. Conversely, inhibition of circPICALM alleviated H/R injury in the HK-2 cell line. The interaction between circPICALM and miR-204-5p was validated through RNA immunoprecipitation and luciferase assay. Finally, circPICALM functioned as a molecular sponge of miR-204-5p and promoted the upregulation of downstream IL-1β expression.</div></div><div><h3>Conclusion</h3><div>CircPICALM plays a critical role in H/R-induced neonatal AKI by sponging miR-204-5p and then activating the downstream IL-1β signaling axis. The inhibition of circPICALM and subsequent suppression of pro-inflammatory factors could serve as a promising biomarker and therapeutic target for early intervention in neonatal AKI.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167795"},"PeriodicalIF":4.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619564","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":"The CNC-family transcription factor NRF3: A crucial therapeutic target for cancer treatment","authors":"Liangwen Yan ,&nbsp;Xinyan Li ,&nbsp;Jiayi Xu ,&nbsp;Shenkang Tang ,&nbsp;Gang Wang ,&nbsp;Mengjiao Shi ,&nbsp;Pengfei Liu","doi":"10.1016/j.bbadis.2025.167794","DOIUrl":"10.1016/j.bbadis.2025.167794","url":null,"abstract":"<div><div>The CNC-bZIP family member NRF3 (NFE2L3) has received limited attention since its discovery. However, recent research has gradually revealed its biological functions, such as involvement in the regulation of cell differentiation, lipid metabolism, and malignant cell proliferation. Under physiological conditions, NRF3 is anchored to the endoplasmic reticulum within the cytoplasm and is biologically inactive. Upon cellular exposure to microenvironmental stresses such as oxidative stress, NRF3 translocates to the nucleus, binds to DNA, and acts as a transcription factor by inducing or repressing the expression of various genes. In terms of tumor regulation, NRF3 exhibits a dual role. It can function as a tumor suppressor to prevent the malignant progression of tumor tissues, protecting the organism from harm. Conversely, current research indicates that NRF3 plays a tumor-promoting role in most tumor tissues. NRF3 enhances the proliferation, migration and invasion of tumor cells by regulating cell cycle-related proteins and enhancing proteasome assembly to degrade tumor suppressors. Studies correlating NRF3 expression with clinical tumor features have found that elevated NRF3 expression is often associated with poor prognoses in various cancers, with patients exhibiting higher NRF3 expression typically having lower survival rates. Several studies suggest that NRF3 could serve as a clinical diagnostic and prognostic marker for tumors. Finally, from the clinical perspective, exploring the feasibility of inhibiting NRF3 activity in tumor treatment provides new insights for the development of NRF3-targeted oncological therapies.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167794"},"PeriodicalIF":4.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619563","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":"Modified expression of JAK-STAT pathway genes in an in vivo rheumatoid arthritis model: A preclinical study to explore genetic insights","authors":"Maham Ghouri ,&nbsp;Nadir Naveed Siddiqui ,&nbsp;Mehreen Lateef ,&nbsp;Lubna Avesi ,&nbsp;Rizma Khan ,&nbsp;Humaira Ghauri ,&nbsp;Ehtisham Asif ,&nbsp;Sitwat Zehra","doi":"10.1016/j.bbadis.2025.167780","DOIUrl":"10.1016/j.bbadis.2025.167780","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by inflammatory synovial tissue, joint deterioration, and effects on systems other than the joints. The biological process underlying the progression of the disease remains unknown, however cell-mediated immunity plays an important part in the onset of RA. The current study investigated the involvement of the JAK-STAT pathway genes (<em>JAK-1</em>, <em>IL-6</em>, and <em>SOCS-2</em>) in the pathogenesis of RA (Rheumatoid arthritis).</div></div><div><h3>Methodology</h3><div>The study was carried out on thirty male Albino Wistar rats categorised in to the three groups. The AIA (Adjuvant induced animal) model was utilised to study the disease pathogenesis. The haematoxylin and Eosin (H and E) was performed followed by ELISA and expression analyses by RT-q-PCR. The obtained data was analysed using one-way ANOVA (Analysis of Variance).</div></div><div><h3>Results</h3><div>Histopathology confirmed that diseased group appeared to be severely impaired, demonstrating manifestations of inflammation with chronic as well as cartilage degenerative changes. Furthermore, chronic inflammation was also noticed in the intertrabecular area. The significant increased levels of JAK1, IL-6 and TYK-2 were recorded among RA group. The gene expression assessment indicated that higher expression of <em>JAK-1</em> and <em>IL-6</em> was linked to the further development of RA in the disease group. The <em>SOSC2</em> (a negative regulator of the JAK-STAT pathway) was significantly (<em>p</em> &lt; 0.01) downregulated. Moreover, <em>SOCS2</em> may be unable to suppress the transcription of the related JAKs (<em>IL-6</em> and <em>JAK-1</em>), resulting in the constant release of immune mediators and contributing to the pathophysiology of RA.</div></div><div><h3>Conclusions</h3><div>The JAK-STAT pathway may serve as the target for diagnosing and treating inflammatory and autoimmune disorders (RA). The findings may enhance therapeutic possibilities by investigating the possible implications of JAK-STAT pathway genes as candidates for progressive rheumatoid arthritis therapies.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167780"},"PeriodicalIF":4.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592597","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":"Overexpression of LMOD1 induces oxidative stress and enhances cell apoptosis of melanoma through the RIG-I like receptor pathway","authors":"Hua Lei ,&nbsp;Linxue Huang ,&nbsp;Huiying Wan,&nbsp;Mingyi Chen","doi":"10.1016/j.bbadis.2025.167762","DOIUrl":"10.1016/j.bbadis.2025.167762","url":null,"abstract":"<div><h3>Background</h3><div>Oxidative stress is crucial in the development of cutaneous melanoma, but its role in melanoma is controversial. We aimed to identify melanoma-associated targets and understand the underlying mechanism.</div></div><div><h3>Methods</h3><div>Differential expressed genes (DEGs) were discovered between control and melanoma samples, and a protein-protein interaction (PPI) network was constructed to find key genes. The prediction accuracy of LMOD1 was assessed by receiver operating characteristic (ROC) curves, and pan-cancer analysis was also performed for LMOD1 expression and immune characteristics. The downstream pathway of LMOD1 was found via KEGG analysis. The effects of LMOD1 on oxidative stress, apoptosis, CD4 + T cells and the downstream pathway were evaluated in melanoma cells and mice.</div></div><div><h3>Results</h3><div>We identified ACTG2, CNN1, LMOD1, MYH11, MYL9, MYLK, TAGLN, TPM1 and TPM2 as melanoma-related DEGs, which could separate control and melanoma samples. The area under curve (AUC) of LMOD1 was &gt; 0.89, indicating high prediction accuracy. LMOD1 expression was decreased in melanoma, and LMOD1 notably correlated with B cells, CD4 T cells, neutrophils, macrophages and dendritic cells (DCs). Overexpression of LMOD1 promoted apoptosis, enhanced migration and invasion, and activated oxidative stress in melanoma cells. LMOD1 promoted apoptosis via activating oxidative stress. The RIG-I-like receptor signaling (RLR) was a downstream pathway of LMOD1. Overexpression of LMOD1 activated oxidative stress, increased apoptosis and CD4 + T cells, and elevated RIG-I and MDA5, while Cyclo (Phe-Pro) (cFP) reversed the results.</div></div><div><h3>Conclusion</h3><div>LMOD1 triggers oxidative stress-mediated apoptosis in melanoma via activating the RLR pathway, which provides promising targets and regulatory pathway for melanoma.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167762"},"PeriodicalIF":4.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579807","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}