Biochemistry and Biophysics Reports最新文献

{"title":"The role of circular RNAs in gastric Cancer: Focusing on autophagy, EMT, and their crosstalk","authors":"Seyedeh Zahra Bakhti ,&nbsp;Saeid Latifi-Navid ,&nbsp;Anahita Dah Pahlevan ,&nbsp;Latifeh Sarabi ,&nbsp;Reza Safaralizadeh","doi":"10.1016/j.bbrep.2025.102169","DOIUrl":"10.1016/j.bbrep.2025.102169","url":null,"abstract":"<div><div>Globally, gastric cancer (GC) is one of the leading causes of cancer-related mortality. GC is a major threat and concern in human societies because of the high degree of metastasis and the lack of primary diagnostic biomarkers. EMT (epithelial‒mesenchymal transmission) and autophagy through different signaling pathways can regulate GC metastasis. There is evidence that there is an association and crosstalk between EMT and autophagy. EMT-related signaling pathways affect the autophagy process. Conversely, depending on the tissue and stage of the tumor, autophagy has a dual role and can induce/inhibit EMT by modulating different signaling networks. Recent research has shown that circular RNAs (circRNAs) can affect autophagy, EMT, and crosstalk by modulating multiple signaling molecules. Thus, elucidating the interplay between EMT and autophagy and the association of circRNAs with these processes could provide new goals for the identification of biomarkers and the treatment of GC. This review comprehensively discusses the impact of EMT and autophagy on the onset and progression of GC, the functional role of circRNAs as inhibitors/activators, their regulatory mechanisms in regulating autophagy and EMT, and their potential applications as diagnostic biomarkers or anti-GC treatments. Thus, repressing EMT with circRNA-based autophagy inhibitor/activator drugs may be a new strategy that provides insights into the treatment of GC.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102169"},"PeriodicalIF":2.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between serum homocysteine and kidney function in hypothyroid patients: A case-control study in Northeast Iran","authors":"Tamara Nagem Faisal ,&nbsp;Mahin Gholipour ,&nbsp;Somayyeh Sadani ,&nbsp;Jahanbakhsh Asadi","doi":"10.1016/j.bbrep.2025.102176","DOIUrl":"10.1016/j.bbrep.2025.102176","url":null,"abstract":"<div><h3>Background/objectives</h3><div>The relationship between serum homocysteine (Hcy) and kidney function in hypothyroidism is not fully understood. This case-control study investigated the association of hyperhomocysteinemia (HHcy) with kidney function tests in patients diagnosed with clinical hypothyroidism (CH).</div></div><div><h3>Methods</h3><div>Forty-five CH cases and 45 matched controls were recruited from a referral clinic in northeast Iran. Serum Hcy was measured using ELISA technology, and Spearman's correlation coefficients were estimated to assess the association between Hcy and various kidney function parameters.</div></div><div><h3>Results</h3><div>In CH patients, the average Hcy level was significantly higher than in those with normal thyroid function (22.63 ± 1.21 vs 12.96 ± 0.24 μmol/L, p = 0.001). Among CH patients, 82.2 % had HHcy (60 % mild, 12.2 % moderate), while only 13.3 % of controls had mild HHcy. Hcy levels were positively correlated with TSH (r = 0.528; p = 0.001), eGFR (r = - 0.418; p = 0.004), urea (r = 0.371; p = 0.012), and creatinine (r = 0.384; p = 0.009) in CH patients. Multivariate logistic regression revealed a significant relationship between Hcy and CH [OR = 2.01, 95 % CI: 1.48–2.72, p = 0.001], even after adjusting for kidney parameters.</div></div><div><h3>Conclusions</h3><div>Serum Hcy was increased with progressive thyroid insufficiency, independent of changes in kidney function, and could be considered a potential risk factor for developing coronary heart disease.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102176"},"PeriodicalIF":2.3,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights on Drug's design against candidiasis on the fructose biphosphate aldolase (Fba1) and the pyruvate kinase (Pk) of Candida glabrata","authors":"Edson E. Maqueda-Cabrera ,&nbsp;Alejandro Castillo-Baltazar ,&nbsp;Nancy A. Vázquez-López ,&nbsp;Maritza Almanza-Villegas ,&nbsp;María Teresa Ramírez-Apan ,&nbsp;M. Carmen Ortega-Alfaro ,&nbsp;José G. López-Cortés ,&nbsp;Abel Moreno ,&nbsp;Mayra Cuéllar-Cruz","doi":"10.1016/j.bbrep.2025.102175","DOIUrl":"10.1016/j.bbrep.2025.102175","url":null,"abstract":"<div><div><em>Candida glabrata</em> is well known to be the second most common cause of invasive candidiasis (IC) within immunocompromised and hospitalized patients, after <em>Candida albicans</em>. <em>Candida</em> species adhere to host cells and implanted medical devices by means of cell wall proteins (CWP), of which the moonlight proteins have recently been described and are of particular importance because they have been identified in response to various virulence and/or pathogenic factors. Among the identified CWP moonlights, fructose-bisphosphate aldolase (Fba1) and pyruvate kinase (Pk) have been observed to confer immune protection against <em>C. albicans</em> and <em>C. glabrata</em> in a mouse model. In other pathogens, these proteins have been used as therapeutic targets. As the treatment of IC has been based on four main drug classes for decades, the <em>Candida</em> species has developed resistance mechanisms. In addition, <em>C. glabrata</em> has an innate resistance to the antifungal drugs, which makes the treatment of IC by this pathogen difficult. It is essential to have new formulations that allow new treatments of patients affected by this pathogen, so new targets with antifungal activity is of primary necessity. For this purpose, in this study we propose the moonlight CWPs Fba1 and Pk as novel candidates for drug targets. Using structural modeling, virtual database analysis, <em>in vitro</em> susceptibility tests, and enzymatic activity assays, we propose the use of new chemical molecules as potential antifungals against <em>C. glabrata</em>. In this sense, we chose to evaluate three chemical molecules (FE1, FE2 and FE3), whose chemical structure gives them the possible molecular leadership against Fba1 and Pk. Through the susceptibility experiments, our data showed that of the three molecules evaluated, FE1 was the best ligand against <em>C. glabrata</em>. We also found that Fba1 and Pk of <em>C. glabrata</em> had the characteristics of therapeutic targets against IC. In the present work, considering a group of tools <em>in silico</em> and experiments <em>in vitro</em> it was possible to identify the best candidate molecule as a possible antifungal for the treatment of IC caused by <em>C. glabrata.</em></div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102175"},"PeriodicalIF":2.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-21-5p inhibitor enhances the radiosensitivity of human cervical cancer cells via blocking CPEB3-mediated CDK1/cyclin B pathway","authors":"Liang Jiao,&nbsp;Yuhua Gao","doi":"10.1016/j.bbrep.2025.102177","DOIUrl":"10.1016/j.bbrep.2025.102177","url":null,"abstract":"<div><div>Currently, radiotherapy remains the standard treatment for human cervical cancer (CC), while approximately 30 % of patients are still non-responsive to radiotherapy, leading to radioresistance. Therefore, it is urgent to discover a novel therapeutic target/biomarker for the radiosensitivity of cervical cancer, and it will be beneficial to clinical guiding significance for individualized treatment of cervical cancer. Herein, the correlation of miR-21-5p and clinicopathological features, clinical efficacy, radiotherapy sensitivity and survival were investigated, and our results showed that miR-21-5p is positively correlated to radio-sensitivity in patients with CC. Furthermore, we found that inhibition of miR-21-5p significantly suppressed the growth of HeLa and SiHa cells, and induced early apoptosis. Meanwhile, miR-21-5p inhibitor caused an arrest cell cycle at G2/M phase. Of note, the miR-21-5p inhibitor significantly enhanced the efficacy of radiation in a dose and timing-dependent manner in human cervical cancer cells. Mechanistically, our results demonstrated that miR-21-5p inhibitior directly up-regulated CPEB3 and further suppressed CDK1/cyclin B pathway. The blockage of CDK1/cyclin B is responsible to the suppression of miR-21-5p and arresting cell cycle at G2/M. Taken together, miR-21-5p can serve as a potential predictor/biomarker for radioresistance and poor prognosis of CC patients. Our results suggested that miR-21-5p inhibitor effectively restored the radio-sensitivity of CC cells through blocking CPEB3-mediated CDK1/Cyclin B pathway.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102177"},"PeriodicalIF":2.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical significance of altered expression of mitochondrial genome-derived LncRNA LIPCAR in colorectal cancer","authors":"Seyed Taha Nourbakhsh ,&nbsp;Fatemeh Mohamadhashem ,&nbsp;Mohammad Mehdi Naghizadeh ,&nbsp;Amirnader Emami Razavi ,&nbsp;Abdolreza Daraei ,&nbsp;Faezeh Mohamadhashem","doi":"10.1016/j.bbrep.2025.102179","DOIUrl":"10.1016/j.bbrep.2025.102179","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence and mortality of colorectal cancer (CRC) are rising; therefore, understanding its molecular pathophysiology is necessary for identifying reliable diagnostic and therapeutic markers. Several studies corroborate the fact that the initiation and progression of various diseases, including cancers, are significantly influenced by the dysregulation of mitochondrial transcripts, such as lncRNAs encoded by the mitochondrial genome. This study is the first to examine the expression profile of LIPCAR in CRC and its correlation with clinicopathological parameters.</div></div><div><h3>Methods</h3><div>In this work, 40 pairs of CRC tissues were obtained, including 40 tumor samples and 40 adjacent non-tumor samples. The SYBR green technique was applied in real-time PCR to analyze the expression profile of LIPCAR in CRC patients.</div></div><div><h3>Results</h3><div>The findings indicated a significant downregulation of LIPCAR in tumor tissue samples compared to adjacent non-tumoral tissues (p-value&lt;.05). Furthermore, no significant relationship between the patients' clinical data and decreased LIPCAR expression was found. Receiver Operating Characteristic (ROC) curve analysis revealed that LIPCAR had an area under the curve (AUC) of .75 (p-value &lt;.0001), with a sensitivity of 87.5 % and a specificity of 57.5 % at a cutoff value of .094.</div></div><div><h3>Conclusion</h3><div>The marked downregulation of LIPCAR expression suggests its critical involvement in the pathogenesis of CRC, potentially functioning as a tumor suppressor. Furthermore, LIPCAR may serve as a clinical biomarker for CRC patients. However, this hypothesis necessitates further validation through comprehensive functional studies conducted both in vitro and in vivo.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102179"},"PeriodicalIF":2.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of SC targeting RhoA regulation and its potential value in gastric cancer therapy","authors":"Haixiu Ma ,&nbsp;Ping Jiang ,&nbsp;Ronghua Ma ,&nbsp;Jing Zhao ,&nbsp;Qi Wang ,&nbsp;Yonghua Xing ,&nbsp;Chengzhu Cao ,&nbsp;Zhanhai Su","doi":"10.1016/j.bbrep.2025.102158","DOIUrl":"10.1016/j.bbrep.2025.102158","url":null,"abstract":"<div><div>RhoA drives the malignant progression of gastric cancer through cytoskeletal remodeling and the regulation of epithelial-mesenchymal transition (EMT). Here, we identified a novel small-molecule inhibitor, (E)-1,9-bis(3,4-dihydroxyphenyl)non-3-en-5-one (SC), targeting RhoA through molecular docking and surface plasmon resonance (SPR) validation. SPR kinetics revealed high-affinity binding (KD = 1.588 μM) with rapid association (ka = 2.769 × 10³ 1/Ms) and slow dissociation (kd = 4.398 × 10⁻³ 1/s), achieving stable SC-RhoA complex formation. In vitro, SC suppressed RhoA expression, in turn upregulating E-cadherin, downregulating N-cadherin and Vimentin, and inhibiting cell migration (<em>p</em> &lt; 0.001). Scanning electron microscopy confirmed pseudopodia retraction and cytoskeletal collapse. Remarkably, oral administration of SC (50 mg/kg/day) attenuated tumor growth in a xenograft model. These results present SC as a potential dual-action RhoA inhibitor that concurrently disrupts GTPase activity and protein stability, offering a promising therapeutic strategy against gastric cancer.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102158"},"PeriodicalIF":2.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix stiffness regulates Mkx expression in rat tenocyte through TRPM7","authors":"Yuta Tsuchiya ,&nbsp;Hikaru Matsuo ,&nbsp;Hiroshi Asahara ,&nbsp;Masafumi Inui","doi":"10.1016/j.bbrep.2025.102178","DOIUrl":"10.1016/j.bbrep.2025.102178","url":null,"abstract":"<div><div>Tendon is the fibrous tissue that connects skeletal muscle and bone, playing a crucial role in transmitting forces generated in muscles to bones and thereby facilitating locomotion. Tendon is continuously subjected to mechanical stimuli, such as tensile force and shear stress, and it is well documented that tendon cells respond to these forces and modulate gene expression and tissue structures. However, whether or how tenocytes respond to matrix stiffness, another key mechanical cue for the tissue, remained elusive. While previous studies have shown that mesenchymal stem cells (MSCs) or tendon derived stem cells (TDSCs) modulate tenogenic gene expression in response to stiffness, its effect on tendon fibroblasts was unclear. In this study, we investigated the role of matrix stiffness on tenocytes derived from tail and Achilles tendon of young rats. Tenocytes displayed stiffness-dependent difference in expression of key tendon-related genes, including Mkx, particularly at 40 kPa stiffness. Interestingly, the transient receptor potential melastatin 7 (TRPM7) channel was identified as an upstream regulator of stiffness-dependent Mkx expression. TRPM7 expression was elevated at 40 kPa stiffness, and its knockdown reduced Mkx expression while abolishing the stiffness-dependent expression pattern. This regulation likely occurs through intracellular calcium (Ca²⁺) and/or magnesium (Mg²⁺) ion influx, as Mkx expression was promoted upon Ca²⁺ ionophore treatment or elevation of extracellular Mg²⁺ concentration. This study underscores the importance of stiffness in tendon biology and adds a novel layer to the transcriptional regulation of Mkx, with implications for understanding tendon development, maintenance, and mechanotransduction.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102178"},"PeriodicalIF":2.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational screening of walnut (Juglans regia) husk metabolites reveals Aesculin as a potential inhibitor of pectate lyase Pel3: Insights from molecular dynamics and τRAMD","authors":"Ali Khakpour ,&nbsp;Negar Ahmadi Shadmehri ,&nbsp;Amir Sedaghati ,&nbsp;Hassan Jamshidian ,&nbsp;Shamim Ghiabi ,&nbsp;Payam Baziyar ,&nbsp;Ehsan Heidari-Soureshjani ,&nbsp;Seyedeh Atefeh Mirahmadi","doi":"10.1016/j.bbrep.2025.102171","DOIUrl":"10.1016/j.bbrep.2025.102171","url":null,"abstract":"<div><div>Pectate lyase (Pel3), an enzyme derived from <em>Clostridium</em> bacteria, plays a significant role in the degradation of pectin and contributes to the spoilage of agricultural products. Pel3 can bind to pectin and break it down, a process that accelerates food decay. Aesculin, a natural compound extracted from walnut husk, has been recognized for its antibacterial and antifungal properties, making it a promising natural inhibitor. The aim of this study was to investigate the inhibitory mechanisms of Aesculin through molecular simulations and random accelerated molecular dynamics (RAMD). Molecular docking results showed that Aesculin may effectively bind to Pel3 and form a strong interaction. RMSD analysis revealed that Aesculin's binding to Pel3 reduced structural fluctuations, thereby enhancing the enzyme's structural stability. Slight changes in the radius of gyration (Rg) indicate a decrease in structural compactness in specific regions of the protein. Furthermore, SASA analysis revealed a modest increase in solvent accessibility. RAMD simulations, performed with 120 replicates, showed a short average residence time (∼0.015 ns), suggesting rapid unbinding and weak interaction at the active site. MM-PBSA analysis yielded a total binding free energy of −2.92 ± 0.44 kcal/mol, mainly driven by van der Waals and electrostatic contributions, confirming moderate and reversible binding. These findings suggest that Aesculin may form alternating interactions with Pel3 as an effective natural inhibitor and exhibit a short residence time in its active site. The molecular dynamics simulations and RAMD analysis suggest that Aesculin can enhance the structural stability of Pel3, presenting it as a potential anti-spoilage agent in the food and agricultural industries.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102171"},"PeriodicalIF":2.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PMab-322: a novel anti-hippopotamus podoplanin monoclonal antibody for multiple applications","authors":"Haruto Yamamoto,&nbsp;Hiroyuki Suzuki,&nbsp;Tomohiro Tanaka,&nbsp;Mika K. Kaneko,&nbsp;Yukinari Kato","doi":"10.1016/j.bbrep.2025.102170","DOIUrl":"10.1016/j.bbrep.2025.102170","url":null,"abstract":"<div><div>Podoplanin (PDPN) is a highly glycosylated type I transmembrane protein. PDPN expression is observed in various normal tissues, including lymphatic endothelial cells, kidney podocytes, and type I alveolar epithelial cells in the lungs. Monoclonal antibodies (mAbs) targeting PDPN across different animal species have facilitated the identification of PDPN-positive cells. To date, we have developed anti-PDPN mAbs for over 20 species. These antibodies suit various applications, including flow cytometry, immunoblotting, and immunohistochemistry. In this study, we generated an anti-hippopotamus PDPN (hipPDPN) mAb, PMab-322 (mouse IgG_2a, kappa), using the Cell-Based Immunization and Screening (CBIS) method. PMab-322 exhibited strong reactivity to hipPDPN-overexpressed Chinese hamster ovary-K1 and demonstrated moderate affinity (<em>K</em>_D: 4.4 × 10⁻⁸ M) in a flow cytometry-based measurement. PMab-322 specifically recognizes hipPDPN but does not cross-react with PDPN from 23 other species. Furthermore, PMab-322 successfully detected hipPDPN in both immunoblotting and immunohistochemistry. These findings highlight the potential of PMab-322 for pathological analyses of hippopotamus-derived tissues.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102170"},"PeriodicalIF":2.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network-based identification of hub transcription factors associated with benzylisoquinoline alkaloid biosynthesis in Papaver somniferum","authors":"Mahsa Eshaghi,&nbsp;Sajad Rashidi-Monfared","doi":"10.1016/j.bbrep.2025.102147","DOIUrl":"10.1016/j.bbrep.2025.102147","url":null,"abstract":"<div><div><em>Papaver somniferum</em> L. (Opium poppy) is one of the world's most economically valuable medicinal plants, and it is the industrial source of essential compounds such as painkillers and other pharmecutical drugs. Recently, large amounts of opium poppy transcriptome data have become accessible in public databases, consisting of data on the different tissues and ecotypes. Despite the importance of this plant, there is little information about the regulatory mechanisms involved in secondary metabolites, especially in benzylisoquinoline alkaloids (BIAs) biosynthesis at the omics level in opium poppy. Herein, we employed co-expression and co-regulation network analysis using Weighted Gene Co-expression Network Analysis (WGCNA) to infer and reveal gene interactions in opium poppy by using RNA-Seq data. To validate possible hub transcription factors (TFs), partial least squares regression (PLS) and Receiver operating characteristic (ROC) analyses were conducted. We identified nine significant co-regulated modules (comprising1501 genes) and hub TF genes related to the biosynthesis of BIAs, including WRKY3, WRKY32, MYB3R-5, bZIP, APRR2, MYB43, MYB82, bHLH, and WRKY40. The results suggest that these hub genes can play a vital role in co-regulating genes involved in secondary metabolic pathways in opium poppy. Also, we detected common regulatory motifs related to hub TFs (WRKY and MYB) of important co-regulated BIA modules. We implied their common regulatory role in the biosynthesis of secondary metabolites in the opium poppy. The results illustrated that co-expressed genes of the modules share common regulatory motifs, especially related to hub TFs of each module, and that they may define their common regulation. ROC analysis with high diagnostic value (AUC = 1) identified the possible role of the hub TF involved in the BIAs pathways. PLS analysis showed a considerable effect of hub TFs (WRKY and bZIP) on the related genes. Our WGCNA analysis at the omics level, along with identifying hub TFs, highlights the regulatory potential of these genes and the primary molecular mechanisms involved in the BIA biosynthetic pathway in opium poppy. These findings provide valuable insights for the regulon engineering of candidate hub TFs in expression systems.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102147"},"PeriodicalIF":2.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}