IF 2.6 3区生物学

Gene Pub Date : 2025-02-10 Epub Date: 2024-12-04 DOI: 10.1016/j.gene.2024.149142

Huihuang Li, Yue Yang, Fan Yang, Xinguo Bao, Chengfu Pan, Weilong Lin, Lianjie Lai, Weimin Lin, Ruiyi Lin

引用次数: 0

Identification of SOX9-related prognostic DEGs and a prediction model for hepatitis C-induced early-stage fibrosis.

IF 2.6 3区生物学

Gene Pub Date : 2025-02-10 Epub Date: 2024-11-30 DOI: 10.1016/j.gene.2024.149133

Haozheng Cai, Junyi Shen, Wei Peng, Xiaoyun Zhang, Tianfu Wen

{"title":"Identification of SOX9-related prognostic DEGs and a prediction model for hepatitis C-induced early-stage fibrosis.","authors":"Haozheng Cai, Junyi Shen, Wei Peng, Xiaoyun Zhang, Tianfu Wen","doi":"10.1016/j.gene.2024.149133","DOIUrl":"10.1016/j.gene.2024.149133","url":null,"abstract":"Background: Hepatitis C virus (HCV) infection induces liver inflammation, activating hepatic stellate cells (HSC) and advancing fibrosis. Studies have indicated that SOX9 overexpression is closely linked to HSC activation. The study aims to identify genes associated with SOX9 and search for potential targets for detecting and treating liver fibrosis.Method: The dataset GSE15654, containing 216 biopsy samples from HCV-induced early-stage cirrhosis patients, was obtained from the GEO database. Prognostic genes were identified through differential gene analysis, LASSO, and Cox regression analyses. CIBERSORT analysis quantified infiltration levels across 22 immune cell types. Constructing a prognostic prediction model using screened genes and conducting preliminary validation using qRT PCR and RNA sequencing techniques.Results: Elevated SOX9 expression correlates with unfavorable outcomes in patients with early-stage liver fibrosis induced by HCV. We identified nine SOX9-related prognostic DEGs in our study. ADAMTS2, ARHGEF5, CCT8, ERG, LBH, FRMD6, INMT, and RASGRF2 were considered risk factors in the disease progression, while DHRS4 was considered a protective factor. SOX9 expression showed a positive correlation with mast cell infiltration, whereas ARHGEF5 and FRMD6 expressions were positively associated with M0 macrophage infiltration. Our combined model surpasses the commonly used APRI and FIB4 indicators in predicting patient prognosis. The testing of clinical samples also preliminarily validated our research results.Conclusion: The prognostic model based on nine SOX9-related DEGs provides an effective tool for forecasting the progression and outcomes of liver fibrosis. This study introduces a new strategy for advancing liver fibrosis prediction and treatment.","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149133"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The melatonin synthase-encoding gene ASMT mediates poplar resistance to drought stress and fungi Dothiorella gregaria.

IF 2.6 3区生物学

Gene Pub Date : 2025-02-10 Epub Date: 2024-12-06 DOI: 10.1016/j.gene.2024.149154

Peizhi Yu, Xia Tang, Banglan Chen, Zihao Chen, Wenli Cui, Yuhang Xing, Ying Li, Fangfang Zhang, Juan B Barroso, Lucas Gutierrez Rodriguez, Yinan Yao, Yongfeng Gao

{"title":"The melatonin synthase-encoding gene ASMT mediates poplar resistance to drought stress and fungi Dothiorella gregaria.","authors":"Peizhi Yu, Xia Tang, Banglan Chen, Zihao Chen, Wenli Cui, Yuhang Xing, Ying Li, Fangfang Zhang, Juan B Barroso, Lucas Gutierrez Rodriguez, Yinan Yao, Yongfeng Gao","doi":"10.1016/j.gene.2024.149154","DOIUrl":"10.1016/j.gene.2024.149154","url":null,"abstract":"In recent years, the increase in extreme climates, such as persistent high temperatures and drought, has adversely affected the growth and development of fast-growing trees. Melatonin (MT) plays an important role in plant responses to biotic and abiotic stresses, yet there is a lack of research on the specific role of limiting enzyme genes for MT biosynthesis in fast-growing woody plants. In this study, we investigated the function of PtoASMT, a key rate-limiting enzyme encoding gene for MT biosynthesis, which can be induced by drought, salt, and the phytohormones ABA, SA and JA. Our results show that: (1) PtoASMT was widely expressed in all tissues of poplar, but was highly expressed in petioles, moderately expressed in roots, stems, shoots and young leaves, exhibiting a typical diurnal expression rhythm in leaves, with the encoded protein localized on chloroplasts; (2) the content of MT was significantly promoted in overexpressing PtoASMT transgenic poplar plants, but there were no obvious differences in their growth and development; (3) overexpressing PtoASMT plants exhibited stronger drought tolerance, accumulating less reactive oxygen species (ROS) under drought stress relative to wild-type plants, whereas knockout PtoASMT plants were more sensitive and accumulated more ROS; (4) overexpressing PtoASMT plants were more resistant to fungi Dothiorella gregaria than WT plants, while knockout plants showed higher sensitivity; meanwhile, the expression of disease resistance-related genes (PRs and JAZ10) was significantly altered. We conclude that PtoASMT enhances the resistance of poplar to drought and Dothiorella gregaria by mediating MT biosynthesis in poplar. These findings contribute to a better understanding the role of ASMT gene in MT accumulation and stress resistance in poplar.","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149154"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative transcriptome analysis and transient assays revealed AaGST and AaBGAL, respectively, contribute to skin and flesh coloration in A. arguta.

IF 2.6 3区生物学

Gene Pub Date : 2025-02-10 Epub Date: 2024-12-04 DOI: 10.1016/j.gene.2024.149143

Xu Zhan, Yukuo Li, Zhe Song, Xiaohan Li, Lingshuai Ye, Miaomiao Lin, Ran Wang, Leiming Sun, Jinbao Fang, Dixin Chen, Xiujuan Qi

{"title":"Comparative transcriptome analysis and transient assays revealed AaGST and AaBGAL, respectively, contribute to skin and flesh coloration in A. arguta.","authors":"Xu Zhan, Yukuo Li, Zhe Song, Xiaohan Li, Lingshuai Ye, Miaomiao Lin, Ran Wang, Leiming Sun, Jinbao Fang, Dixin Chen, Xiujuan Qi","doi":"10.1016/j.gene.2024.149143","DOIUrl":"10.1016/j.gene.2024.149143","url":null,"abstract":"Actinidia arguta possesses different colors in the fruit skin and flesh, but the underlying mechanism has not yet been clarified. In this study, we conducted 36 samples RNA-seq to investigate the phenotypic expression of different fruit tissues (skin and flesh) in red and green A. arguta varieties during different coloring phases. GO and KEGG enrichment results of differentially expressed genes (DEGs) suggested that the red color of the skin and flesh was derived from anthocyanin transport and flesh softening, respectively. Weighted gene co-expression network analysis (WGCNA) revealed MEyellow and MEblack modules significantly correlated with skin and flesh coloration, and two genes, Glutathione S-transferases (AaGST) and β-galactosidases (AaBGAL), were identified as hub genes involved in different tissue-specific coloration. Transient overexpression in apples and kiwifruits confirmed the role of AaGST and AaBGAL in color formation. Our results preliminarily explore the mechanism of red color formation in different A. arguta fruit tissues and provide novel insights into red color formation.","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149143"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

miR-6760-5p suppresses neoangiogenesis by targeting Yes-associated protein 1 in patients with moyamoya disease undergoing indirect revascularization.

IF 2.6 3区生物学

Gene Pub Date : 2025-02-10 Epub Date: 2024-12-09 DOI: 10.1016/j.gene.2024.149152

Yunyu Wen, Junda Chen, Tinghan Long, Fangzhou Chen, Zhibin Wang, Siyuan Chen, Guozhong Zhang, Mingzhou Li, Shichao Zhang, Huibin Kang, Wenfeng Feng, Gang Wang

{"title":"miR-6760-5p suppresses neoangiogenesis by targeting Yes-associated protein 1 in patients with moyamoya disease undergoing indirect revascularization.","authors":"Yunyu Wen, Junda Chen, Tinghan Long, Fangzhou Chen, Zhibin Wang, Siyuan Chen, Guozhong Zhang, Mingzhou Li, Shichao Zhang, Huibin Kang, Wenfeng Feng, Gang Wang","doi":"10.1016/j.gene.2024.149152","DOIUrl":"10.1016/j.gene.2024.149152","url":null,"abstract":"Objective: The aim of this research was to investigate the specific regulatory role of miR-6760-5p in angiogenesis in moyamoya disease.Methods: HUVECs were transfected with miR-6760-5p inhibitor and mimics fragments, then subjected to assays for cell proliferation, migration, and tube formation. Subsequently, downstream target genes of miR-6760-5p were predicted and the protein expression levels of these genes were evaluated. The presence of miR-6760-5p and YAP1 was verified by a dual luciferase reporter gene test, followed by an assessment of the effects of YAP1 and miR-6760-5p on the HUVECs.Results: Comparatively to the control group, increased expression of miR-6760-5p decreased cell growth, movement, and tube formation. YAP1 gene was discovered as a target controlled by miR-6760-5p, with subsequent investigation confirming YAP1 as a gene regulated by miR-6760-5p. Additionally, miR-6760-5p was found to counteract the angiogenesis-promoting effect of YAP1.Conclusion: The results of this research suggest a possible link between the miR-6760-5p gene found in the cerebrospinal fluid of individuals with moyamoya disease and the process of vascularization in this particular condition. The findings indicate that miR-6760-5p may be a new molecular indicator and potential target for the diagnosis of moyamoya disease.","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149152"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SLC12A9 is an immunological and prognostic biomarker for glioma.

IF 2.6 3区生物学

Gene Pub Date : 2025-02-10 Epub Date: 2024-11-30 DOI: 10.1016/j.gene.2024.149136

Danting Li, Peilin Zheng, Shoujun Huang

{"title":"SLC12A9 is an immunological and prognostic biomarker for glioma.","authors":"Danting Li, Peilin Zheng, Shoujun Huang","doi":"10.1016/j.gene.2024.149136","DOIUrl":"10.1016/j.gene.2024.149136","url":null,"abstract":"Background: Glioma is one of the most common malignant brain tumors. It has a high rate of progression and a poor prognosis, and effective biomarkers still need to be identified. The solute carrier family 12 (SLC12) family has been reported to be involved in various physiological and pathological processes, but their functional roles in glioma remain unclear.Methods: Using public datasets, we studied the mutation and expression level of SLC12 family genes in glioma and identified the significantly differentially expressed member solute carrier family 12 member 9 (SLC12A9). We further predicted the prognostic role of SLC12A9 in glioma by using the Kaplan-Meier method and Cox regression analysis. Then, we performed biological functional enrichment analysis. We focused on the relationships between SLC12A9 expression and immune infiltration in glioma. Meanwhile, we conducted in vitro experiments to evaluate the effect of SLC12A9 expression on glioma cells.Results: Among the members of the SLC12 family, SLC12A9 had the highest mutation rate in glioma, with gene amplification as the major mutation type, and its expression was significantly upregulated in glioma. Higher SLC12A9 expression was significantly associated with older age, higher grade, wild-type isocitrate dehydrogenase (IDH), and a worse prognosis. The functional enrichment analysis indicated that SLC12A9 is mainly related to ion channel annotation. Gene set enrichment analysis (GSEA) revealed that SLC12A9 was mainly related to the DNA replication pathway. Furthermore, we found that SLC12A9 correlated with tumor-infiltrating immune cells and immune checkpoints. Thus, SLC12A9 may be involved in regulating the immune response of glioma. Finally, our in vitro experiments revealed that silencing SLC12A9 dramatically inhibited glioma cell growth and migration.Conclusions: We showed that SLC12A9 may be a new predictive biomarker for glioma diagnosis, prognosis, and immunotherapy response, offering helpful guidelines to advance glioma treatment.","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149136"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A comprehensive analysis of the pyruvate kinase M1/2 (PKM) in human cancer.

IF 2.6 3区生物学

Gene Pub Date : 2025-02-10 Epub Date: 2024-12-07 DOI: 10.1016/j.gene.2024.149155

Shuaishuai Xue, Ziyi Luo, Yangqi Mao, Siyuan Liu

{"title":"A comprehensive analysis of the pyruvate kinase M1/2 (PKM) in human cancer.","authors":"Shuaishuai Xue, Ziyi Luo, Yangqi Mao, Siyuan Liu","doi":"10.1016/j.gene.2024.149155","DOIUrl":"10.1016/j.gene.2024.149155","url":null,"abstract":"Background: Pyruvate Kinase Muscle Isozyme (PKM), as a member of the pyruvate kinase, is a key enzyme in glycolysis. Numerous tumors have demonstrated its oncogenic properties. There is, however, no pan-carcinogenic analysis for PKM.Methods: A thorough analysis of PKM across various types of cancer was carried out using bioinformatics resources like The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) database. This study involved analyzing the role of PKM in 33 various types of cancers, along with investigating gene expressions, survival rates, clinical importance, genetic changes, immune system presence, and related signaling pathways. Furthermore, we evaluated the effects of PKM knockdown on human colon carcinoma, and glioblastoma cell lines by in vitro experimentation.Results: In most tumors, PKM expression was markedly increased and was associated with unfavorable overall survival (OS) in certain individuals. In addition, infiltration of macrophages was associated with PKM expression in various tumors. PKM was linked to glycolysis/gluconeogenesis, HIF-1 signaling, carbon metabolism, and NADPH regeneration in a mechanistic manner. Additionally, cell experiments showed that the knockdown of PKM could reduce the proliferation and migration abilities while promoting the apoptosis of Caco-2, and U-87 MG cells.Conclusion: PKM controls immune cell infiltration, impacts patient outcomes in various types of cancer, and plays an essential role in proliferation and migration in some tumor cells by affecting glycometabolism. The PKM molecule may serve as a potential prognostic biomarker and therapeutic target for human cancers.","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149155"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Copy number variations of stepwise-selected doxorubicin-resistant MCF-7 cell lines.

IF 2.6 3区生物学

Gene Pub Date : 2025-02-10 Epub Date: 2024-12-03 DOI: 10.1016/j.gene.2024.149139

Hasan Huseyin Kazan, İrem Sinem Acınan, Başak Kandemir, Ceyhan Pırıl Karahan, Gülsüm Kayhan, Özlem Darcansoy İşeri

{"title":"Copy number variations of stepwise-selected doxorubicin-resistant MCF-7 cell lines.","authors":"Hasan Huseyin Kazan, İrem Sinem Acınan, Başak Kandemir, Ceyhan Pırıl Karahan, Gülsüm Kayhan, Özlem Darcansoy İşeri","doi":"10.1016/j.gene.2024.149139","DOIUrl":"10.1016/j.gene.2024.149139","url":null,"abstract":"Elimination of cytotoxic effect in cells with multidrug resistance (MDR) phenotype is a situation that is gradually acquired over time and develops through multiple pathways resulting in global phenotypic changes of cells. Although molecular background of the resistance phenotype has widely been studied in the gene expression level, segmental and gene copy number variations (CNVs) have limitedly been documented. Thus, in the present study, we aimed to analyze the CNVs using DNA microarray in the sensitive and two doxorubicin-resistant MCF-7 breast cancer cell lines which had different resistance indices. In the present study, we performed conventional karyotyping and array comparative genomic hybridization (aCGH). Then, results of aCGH data were studied with genomic profiling, comparison analysis and ideogram plotting to evaluate genomic profiles, and the loss and gains of heterozygosity profiles. Next, gene lists for each cell line were compared with the 66-breast cancer-related genes and the multidrug resistance-related genes. aCGH analyses showed that CNV profiles and the copy number of specific genes were dramatically different between these three cell lines. Totally, 6212, 6558, and 11,201 genes were found to be altered in MCF-7, MCF-7/400DOX, and MCF-7/1000DOX genomes, respectively. Amongst the MCF-7/1000DOX had the highest number of altered genes, and doxorubicin resistance may cause differential chromosomal changes depending on the resistance status. DNA microarray would be one of the informative methods used in the studies on the cancer drug resistance in addition to transcriptomic and proteomic level high throughput analysis to define molecular mechanisms of the resistance status.","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149139"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synergistic toxicity of compound heterozygous mutations in the COL4A3 gene causes end-stage renal disease in A large family of Alport syndrome.

IF 2.6 3区生物学

Gene Pub Date : 2025-02-10 Epub Date: 2024-11-29 DOI: 10.1016/j.gene.2024.149132

Longxin Xie, Yuxi Ding, Ying Qiu, Yi Shi

{"title":"Synergistic toxicity of compound heterozygous mutations in the COL4A3 gene causes end-stage renal disease in A large family of Alport syndrome.","authors":"Longxin Xie, Yuxi Ding, Ying Qiu, Yi Shi","doi":"10.1016/j.gene.2024.149132","DOIUrl":"10.1016/j.gene.2024.149132","url":null,"abstract":"Alport syndrome (AS) is a genetic disorder characterized by kidney disease and hearing/vision abnormalities, resulting from mutations in the COL4A3, COL4A4, or COL4A5 genes. While numerous mutations have been identified in AS cases, the precise molecular mechanisms, particularly for compound mutations, remain under investigation. This study investigated the molecular mechanisms of AS in a proband with end-stage kidney disease (ESKD) using whole exome sequencing, which identified two compound heterozygous COL4A3 missense mutations: NM_000091.5:c.1354G > A (p.G452R) and NM_000091.5:c.4793 T > G (p.L1598R). Sixteen family members of the proband were genotyped, and further analyses, including in silico structural prediction, molecular docking, and in vitro co-immunoprecipitation assays, revealed that the p.G452R mutation disrupted the collagen triple helical structure, associated with hematuria in carriers, while the p.L1598R mutation interfered with the interaction between the NC1 domains of COL4A3 and COL4A4 proteins, crucial for collagen trimerization. These findings demonstrate a synergistic loss-of-function effect of the two mutations, contributing to the AS pathogenesis in the proband, and emphasize the importance of genetic screening and personalized treatment strategies for AS.","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149132"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MicroRNA-34a-5p regulates agouti-related peptide via krüppel-like factor 4 and is disrupted by bisphenol A in hypothalamic neurons.

IF 2.6 3区生物学

Gene Pub Date : 2025-02-10 Epub Date: 2024-11-29 DOI: 10.1016/j.gene.2024.149129

Minyi Yu, Wenyuan He, Denise D Belsham

{"title":"MicroRNA-34a-5p regulates agouti-related peptide via krüppel-like factor 4 and is disrupted by bisphenol A in hypothalamic neurons.","authors":"Minyi Yu, Wenyuan He, Denise D Belsham","doi":"10.1016/j.gene.2024.149129","DOIUrl":"10.1016/j.gene.2024.149129","url":null,"abstract":"Obesity is a complex disease marked by increased adiposity and impaired metabolic function. While diet and lifestyle are primary causes, endocrine-disrupting chemicals (EDCs), such as bisphenol A (BPA), significantly contribute to obesity. BPA, found in plastic consumer products, accumulates in the hypothalamus and dysregulates energy homeostasis by disrupting the neuropeptide Y (NPY)/agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) neurons. However, the precise molecular mechanisms of how BPA disrupts neuropeptide expression remains unclear. We hypothesized that microRNAs (miRNAs), which regulate approximately 60% of the human protein-coding genome and are crucial for hypothalamic energy regulation, may mediate the effects of BPA on Agrp. Using the TargetScanMouse 8.0 and DIANA microT bioinformatics tools, we identified miR-501-5p as a potential miRNA that directly regulates Agrp and the miR-34 family as miRNAs that indirectly regulate Agrp through its transcription factor krüppel-like factor 4 (KLF4). We found that in an immortalized NPY/AgRP-expressing cell line, mHypoE-41, miR-501-5p unexpectedly upregulated Agrp, while miR-34a-5p reduced Klf4 and Agrp mRNA levels. Serum starvation reduced miR-34a-5p levels and elevated Agrp mRNA levels, suggesting a potential role in AgRP regulation. Inhibiting the miR-34a-5p interaction with the Klf4 3'UTR using a specific target site blocker prevented the downregulation of both Klf4 and Agrp, suggesting miR-34a-5p alters Agrp mRNA levels via regulation of KLF4. BPA treatment increased Agrp and Klf4 expression while simultaneously decreasing miR-34a-5p levels, indicating miR-34a-5p may play a role in BPA-mediated dysregulation of Agrp. Overall, this study highlights indirect miRNA-based regulation of Agrp, which can also be dysregulated by obesogens, such as BPA.","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149129"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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