Acta biochimica et biophysica Sinica最新文献

{"title":"Inhibition of the cGAS-STING pathway mitigates liver injury induced by docetaxel-carboplatin neoadjuvant chemotherapy via autophagy promotion.","authors":"Song Hu, Linghui Kong, Mo Chen, Cheng Teng, Ying Zhao, Xiaohong Yuan, Shunv Cai, Xiaoyan Zhu, Pingbo Xu","doi":"10.3724/abbs.2026094","DOIUrl":"10.3724/abbs.2026094","url":null,"abstract":"<p><p>The docetaxel-carboplatin (TCb) combination is a widely used neoadjuvant chemotherapy regimen, yet its clinical application is frequently accompanied by hepatotoxicity and drug-induced liver injury (DILI). However, the underlying molecular mechanisms remain incompletely understood. This study investigates the role of cGAS-STING-mediated autophagy in TCb-induced DILI. A TCb-induced DILI mouse model is established by intraperitoneal administration of docetaxel (10 mg/kg) and carboplatin (50 mg/kg) once weekly for two weeks, alongside an <i>in vitro</i> AML12 hepatocyte model (docetaxel 20 μM + carboplatin 100 μM). Liver injury, apoptosis, autophagy, and cGAS-STING signaling are evaluated using histopathological staining, biochemical assays, RT-qPCR, western blotting, immunofluorescence, and immunohistochemistry. TCb treatment induces significant liver injury, as evidenced by elevated serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL), histopathological damage, and increased collagen deposition. TCb markedly promotes hepatocyte apoptosis, characterized by increased expression of Bcl-2 associated X protein (BAX) and decreased expression of Bcl-2. Concomitantly, TCb suppresses basal autophagy, as indicated by p62 accumulation, reduced Beclin-1 expression, decreased LC3-II/I ratio, and diminished autophagosome formation. Mechanistically, TCb robustly activates the cGAS-STING pathway, accompanied by enhanced phosphorylation of TBK1 and IRF3. Notably, pharmacological inhibition of STING with C-176 or siRNA-mediated <i>STING</i> knockdown restores autophagic flux and significantly attenuates TCb-induced apoptosis. Collectively, these findings suggest that sustained activation of the cGAS-STING pathway contributes to TCb-induced DILI by impairing autophagic homeostasis and promoting hepatocyte apoptosis. Targeting cGAS-STING-mediated autophagy represents a potential therapeutic strategy for preventing chemotherapy-associated hepatotoxicity.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":"Vol. 1","pages":"fpage-lpage"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148051869","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":"MAL2 drives hepatocellular carcinoma progression by recruiting regulatory T cells via CCL22 and inducing the immunosuppressive microenvironment.","authors":"Qian Zhang, Xiaowei Sun, Lantian Zhang, Tianyi Ni, Yingying Wang, Liying Tu, Wei Yan, Weiwei Tang, Xuehao Wang","doi":"10.3724/abbs.2026095","DOIUrl":"10.3724/abbs.2026095","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, necessitating the identification of novel therapeutic targets. The transmembrane protein MAL2 has been implicated in various cancers, but its functional role and mechanistic underpinnings in HCC are not fully understood. To comprehensively understand its role in HCC, we analyze public single-cell RNA sequencing (scRNA-seq) data and find that MAL2 is significantly enriched in malignant HCC cells. <i>In vitro</i>, <i>MAL2</i> is stably knocked down by shRNA in Hep-3B and HCC-LM3 cell lines, and functional experiments including colony formation, EdU, transwell, and wound healing assays demonstrate that <i>MAL2</i> depletion markedly suppresses proliferation, invasion, and migration of HCC cell lines. <i>In vivo</i>, a subcutaneous tumor model using H22 cells reveals that <i>MAL2</i> knockdown inhibits tumor growth, accompanied by reduced Ki-67 level and increased apoptosis. Further analysis via mass cytometry indicates that MAL2 downregulation reshapes the immune microenvironment, notably reducing CD4 ⁺ T cells, Tregs, CD8 ⁺ T cells, and exhaustion markers (PD-L1, PD1, and TIGIT) while increasing B cells and myeloid-derived suppressor cells (MDSCs). Mechanistically, ELISA and immunofluorescence staining validate that <i>MAL2</i> knockdown impairs the secretion of CCL22, a chemokine known for recruiting Tregs, leading to reduced Treg recruitment and decreased production of the immunosuppressive cytokines IL-10 and TGF-β. In conclusion, MAL2 drives HCC progression by promoting tumor cell proliferation, invasion, and immunosuppression through CCL22-mediated Treg recruitment, positioning MAL2 as a promising therapeutic target to counteract tumor growth and remodel the immunosuppressive microenvironment in HCC.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":"58 6","pages":"1-14"},"PeriodicalIF":4.5,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148051818","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":"CCAR2 reduces the number of osteoclasts by controlling osteoclast apoptosis.","authors":"Junyue Zhang, Yiping Song, Si Chen, Kyu Yun Jang, Jung Ryul Kim, Young Jae Moon","doi":"10.3724/abbs.2026052","DOIUrl":"10.3724/abbs.2026052","url":null,"abstract":"<p><p>Estrogen-associated signals regulating osteoclast apoptosis control osteoclast numbers. Enhancing anti-apoptotic activity during M-CSF and RANKL stimulation, which promotes osteoclast differentiation, increases the number of osteoclasts. Cell cycle and apoptosis regulator 2 (CCAR2) significantly modulates cancer cell survival and apoptosis by interacting with estrogen receptor α (ERα). Because CCAR2 regulates cell fate through ERα, we hypothesize that CCAR2 may inhibit the formation of bone-resorbing osteoclasts. We screen a public database of inbred mouse strain information to identify correlations between <i>Ccar2</i> mRNA expression in bone and bone mineral density (BMD). We find that <i>Ccar2</i> expression correlates positively with femoral and spine BMD. In addition, an increased abundance of osteoclasts is observed in aged mice, but the expression of CCAR2 in osteoclasts is lower in old mice than in young mice. To identify the role of CCAR2 in osteoclasts, we generate <i>CCAR2</i>-knockout (KO) RAW 264.7 cells using CRISPR-Cas9. The <i>CCAR2</i>-KO cells exhibit increased osteoclast numbers, reduced intracellular ROS levels, and decreased apoptosis during M-CSF- and RANKL-induced osteoclastogenesis. Mechanistically, CCAR2 binds to ERα, altering its nuclear translocation and increasing apoptotic transcriptional activity. These findings suggest that CCAR2 inhibits osteoclast numbers by increasing ERα-mediated apoptosis.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":"xx xx","pages":"xx"},"PeriodicalIF":4.5,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148051901","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":"SGLT2 inhibitor dapagliflozin treats heart failure with preserved ejection fraction via the SIRT1/PGC-1α pathway.","authors":"Shiwen Zhang, Yansong Cui, Jingwen Chen, Shuaishuai Zhou, Yujiao Zhang, Kuan Li, Yinglong Hou","doi":"10.3724/abbs.2026078","DOIUrl":"10.3724/abbs.2026078","url":null,"abstract":"<p><p>Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated clinical benefits in heart failure with preserved ejection fraction (HFpEF), yet the underlying mechanisms remain poorly defined. Given that mitochondrial dysfunction represents a central feature of HFpEF pathophysiology, we investigate whether modulation of mitochondrial homeostasis contributes to the cardioprotective effects of dapagliflozin. Using a Dahl salt-sensitive rat model of HFpEF, we find that dapagliflozin markedly improves diastolic function and attenuates cardiac hypertrophy, fibrosis, and apoptosis. These beneficial effects are accompanied by significant restoration of mitochondrial structure and function. Consistently, in an <i>in vitro</i> HFpE model, dapagliflozin enhances mitochondrial respiratory capacity in cardiomyocytes, indicating a direct mitochondrial regulatory effect. Mechanistically, integrative transcriptomic and experimental analyses identify the SIRT1/PGC-1α/Mitofusin-2 (Mfn-2) signaling axis as a critical pathway suppressed in HFpEF but reactivated following dapagliflozin treatment. Activation of this pathway promotes mitochondrial biogenesis and improves mitochondrial dynamics, thereby preserving cardiomyocyte homeostasis. Collectively, our findings reveal that dapagliflozin exerts cardioprotective effects in HFpEF by restoring mitochondrial homeostasis through the SIRT1/PGC-1α/Mfn-2 axis, providing mechanistic insight into SGLT2i-mediated benefits and highlighting mitochondrial regulation as a potential therapeutic strategy for HFpEF.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":"xx xx","pages":"1624-1636"},"PeriodicalIF":4.5,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148051845","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":"USP18-stabilized ELF3 drives glycolysis and malignant progression in lung adenocarcinoma.","authors":"Yu Zeng, Yeran Yi, Qinfen Zhang, Li Li, Xiaohe Zhao, Haixia Jin, Ziqi Huang, Shiwei Guo, Qiyu Wang, Meng Shen, Baihui Li, Lili Yang, Weipeng Zhao","doi":"10.3724/abbs.2026082","DOIUrl":"10.3724/abbs.2026082","url":null,"abstract":"<p><p>E74-like ETS transcription factor 3 (ELF3) has been implicated in various tumorigenesis and inflammatory diseases. However, its expression profile and role in lung adenocarcinoma (LUAD) remain poorly defined. In the present study, through comprehensive clinical and experimental analyses, we aim to clarify the association between <i>ELF3</i> overexpression in LUAD tissues and poor prognosis. Functional assays reveal that <i>ELF3</i> knockdown inhibits the proliferation, migration, and invasion of LUAD cells, while ELF3 overexpression enhances these functions. Pathway enrichment analysis indicates that ELF3 influences the metabolic processes of LUAD. Mechanistically, ELF3 exerts oncogenic effects by regulating the transcription of hexokinase 2 (HK2) and glucose transporter type 1 (GLUT1). High-throughput screening reveals that dacinostat, by targeting the active site of the ELF3 protein, attenuates the glycolytic, proliferative, and metastatic abilities of LUAD cells. Additionally, ubiquitin-specific peptidase 18 (USP18) strengthens the stability of the ELF3 protein and influences the malignant biological behavior of LUAD through ELF3. In conclusion, the USP18/ELF3/HK2 and USP18/ELF3/GLUT1 axes play critical roles in glucose metabolism, proliferation, and metastasis of LUAD cells. Dacinostat inhibits the malignant progression of LUAD by targeting ELF3, providing strong evidence for developing novel therapeutic strategies targeting ELF3.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":"58 6","pages":"1-17"},"PeriodicalIF":4.5,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148051840","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":"Curcumin suppresses head and neck squamous cell carcinoma progression via NCOA4-FTH1-mediated ferroptosis.","authors":"Yao Liu, Junli Ning, Zegang Li, Hong Yang, Xin Li, Zhangyong Tang, Deng Shiwu, Ye Zhao, Ge Zhang","doi":"10.3724/abbs.2026090","DOIUrl":"https://doi.org/10.3724/abbs.2026090","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) remains a prevalent malignancy with limited therapeutic options. Ferroptosis is an iron-mediated type of programmed cell death, and it has surfaced as a viable oncology treatment approach. Curcumin (Cur) is a natural polyphenol that exhibits potent anti-tumor properties; however, the underlying molecular mechanisms regarding cell death modalities in HNSCC remain underexplored. The results of this study show that Cur is an effective ferroptosis inducer in HNSCC based on transcriptomic sequencing analysis. Cur treatment triggers hallmark ferroptosis characteristics that include iron accumulation, lipid peroxidation, radical oxygen species generation, and mitochondrial damage. These effects are all reversed by the ferroptosis inhibitor ferrostatin-1. Furthermore, we discover that Cur promotes the lysosomal degradation of ferritin heavy chain 1 (FTH1). Specifically, Cur enhances the interaction between the cargo receptor, nuclear receptor coactivator 4 (NCOA4), and FTH1, facilitating ferritinophagy. <i>NCOA4</i> knockdown blocks FTH1 degradation and rescues HNSCC cells from Cur-induced ferroptosis. These results demonstrate that Cur triggers ferroptosis in HNSCC through NCOA4-mediated ferritinophagy. The results of this study highlight the NCOA4-FTH1 axis as a promising therapeutic target and support Cur as a potential candidate for HNSCC treatment.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148215643","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":"Synergistic hepatic metabolic effects induced by coexposure to the fungicides carbendazim and procymidone in rats.","authors":"Zhiwei Bao, Ting Luo, Shiyi Hu, Guiling Yang, Yuanxiang Jin","doi":"10.3724/abbs.2026041","DOIUrl":"10.3724/abbs.2026041","url":null,"abstract":"<p><p>Carbendazim (CBZ) and procymidone (PRO) are two fungicides widely used for decades. With excessive use, potential public health risks from their coresidues in vegetables and the environment have attracted increasing attention. Here, 6-week-old male SD rats are orally gavaged with 200 mg/kg CBZ, 200 mg/kg PRO, or 200 mg/kg CBZ + 200 mg/kg PRO (Mix group). At 1, 8 and 72 h postexposure, liver samples were collected and subjected to untargeted metabolomic analysis. Sparse partial least squares discriminant analysis (sPLS-DA) shows that all treatment groups exhibit significant separation from the Control group. Meanwhile, the Mix group is also significantly separated from the individual treatment groups. At 1 and 8 h postexposure, differentially abundant metabolites are predominantly enriched in fatty acyls according to HMDB classification, and the levels of 12-keto-eicosatetraenoic acid (12-KETE) are significantly elevated across treatment groups. 12-KETE acts as a PPARγ ligand and regulates PPARγ signaling pathways. The Mix-8 h group exhibits the largest number of differentially abundant metabolites. KEGG enrichment analysis identifies two uniquely enriched pathways with high impact (phenylalanine, tyrosine and tryptophan biosynthesis and linoleic acid metabolism). Within these pathways, linoleic acid, 13(S)-HPODE and L-tyrosine are significantly decreased only in the Mix-8 h group. Time-course analysis reveals diverse patterns of altered differentially abundant metabolites rather than a simple monotonic trend. Additionally, hepatic metabolite profiles remain separated among treatment groups after 72 h postexposure, although CBZ and PRO residues are hardly detected. Collectively, these results indicate that coexposure to CBZ and PRO amplifies hepatic metabolic disruption and produces mixture-specific toxic effects.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":"Vol. 1","pages":"fpage-lpage"},"PeriodicalIF":4.5,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148051893","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":"Targeting lactate with a GLUT1 inhibitor reverses PARP inhibitor resistance in ovarian cancer.","authors":"Shuqi Nie, Congli Pu, Hongyu Liu, Xuan Pei, Yi Wang, Xiaohang Lu, Yufan Cheng, Wei Jiang, Huijuan Yang","doi":"10.3724/abbs.2025249","DOIUrl":"10.3724/abbs.2025249","url":null,"abstract":"<p><p>The widespread application of PARP inhibitors (PARPis) in epithelial ovarian cancer has led to the emergence of therapy resistance as a critical clinical challenge. To investigate the underlying mechanisms, we perform RNA sequencing of paired patient samples obtained before and after PARPi treatment, revealing a significant upregulation of glycolytic activity following therapy. Olaparib-resistant OVCAR8 and A2780 cells are established by exposure to increasing concentrations of Olaparib, and pharmacological inhibition or knockdown of <i>GLUT1</i> restores Olaparib sensitivity, with synergistic effects confirmed in patient-derived organoids and xenograft models. Mechanistically, GLUT1 suppression reduces lactate accumulation, subsequently impairing tumor proliferation and DNA repair capacity through downregulation of the DNA repair protein MRE11. These findings establish lactate as a key mediator of PARPi resistance and propose targeting lactate metabolism as a promising combination strategy to improve PARPi efficacy in advanced ovarian cancer.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":"xx xx","pages":"xx"},"PeriodicalIF":4.5,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148051884","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":"Targeting the Spata13-TGFβRI interaction inhibits infection-driven capsular contracture via suppression of fibroblast activation.","authors":"Yiyin Tang, Jiaqian Liao, Qi Tang, Xi Wang, Nan Lan, Yao Ji, Hailei Wang, Yunchao Huang, Dequan Liu, Binbin Yang, Ping Zhao","doi":"10.3724/abbs.2026077","DOIUrl":"https://doi.org/10.3724/abbs.2026077","url":null,"abstract":"<p><p>Capsular contracture, a common complication following breast implant surgery, is driven by fibroblast-to-myofibroblast transition and excessive collagen deposition. Although bacterial biofilm and TGF-β signaling are implicated, the molecular mechanisms linking infection to fibrosis remain unclear. Using <i>in vitro</i> fibroblast models and <i>in vivo</i> rat capsular contracture assays, we combine transcriptomics, protein interaction analysis, and targeted mutagenesis to identify Spata13 as a critical mediator of TGF-β/Smad signaling. Functional assays assess collagen synthesis (hydroxyproline content), fibroblast proliferation (CCK-8), and myofibroblast markers (α-SMA). A competitive peptide (PT637) is designed to disrupt Spata13-TGFβRI binding. <i>Staphylococcus epidermidis</i> biofilm synergizes with silicone implants to upregulate Spata13, activates TGF-β/Smad signaling, and promotes fibroblast activation. Spata13 binds to TGF-β receptor I (TGFβRI) via Ser637, and its knockdown suppresses α-SMA expression and collagen deposition. The TGFβRI inhibitor LY2157299 attenuates fibrosis <i>in vivo</i>. Strikingly, PT637 disrupts the Spata13-TGFβRI interaction and reduces both fibrosis markers and capsular thickness in biofilm-challenged rats. We define Spata13 as a novel regulator of infection-associated fibrosis and demonstrate that targeted disruption of Spata13-TGFβRI binding by PT637 offers a precision therapeutic strategy for capsular contracture.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203749","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":"Sulforaphane promotes mammary epithelial cell proliferation in Xizang sheep by increasing FOXM1 and PI3K-Akt signaling.","authors":"Zhenzhen Zhang, Tingxian Chen, Yangzong Zhaxi, Jiacuo Jinmei, Wangjie Zhaxi, Quzhu Yixi, Zhen Yang, Wangsheng Zhao, Tianzeng Song","doi":"10.3724/abbs.2026040","DOIUrl":"10.3724/abbs.2026040","url":null,"abstract":"<p><p>Mammary epithelial cells (MECs) are crucial for milk synthesis and secretion, and their abundance and activity directly influence milk yield and quality. This study investigates the effects of sulforaphane (SFN) on MECs isolated from Xizang Sewa sheep. The findings reveal that SFN at a concentration of 5 μM promotes cell proliferation, enhances DNA synthesis, facilitates the G1/S phase transition, and increases the expression levels of critical cell cycle regulators such as <i>Ki67</i>, <i>PCNA</i>, <i>CDK4</i>, <i>CCNE1</i>, <i>CCNA2</i>, and <i>CCND2</i>. RNA-sequencing analysis further confirms the modulation of numerous genes involved in cell cycle regulation, including <i>FOXM1</i>. Further investigation into <i>FOXM1</i> demonstrates that its inhibition results in a significant reduction in the mRNA and protein levels of various cell cycle regulatory genes induced by SFN, including <i>Ki67</i>, <i>PCNA</i>, <i>CDK4</i>, and <i>CCNE1</i>. Furthermore, treatment with a PI3K-Akt signaling inhibitor (LY294002) leads to a decrease in PI3K-Akt signaling activity, concomitant with reduced levels of <i>PCNA</i> and <i>FOXM1</i>. However, these effects are ameliorated following SFN treatment. These findings suggest that SFN may significantly enhance cell proliferation of MECs in sheep by upregulating <i>FOXM1</i> expression and activating the PI3K-AKT signaling pathway. This study identifies a promising pharmacological target for augmenting milk production in sheep.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":"xx xx","pages":"xx"},"PeriodicalIF":4.5,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136018","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}