Gene Reports最新文献

{"title":"Expression of MMP-11, an estrogen-suppressed gene in MCF-7 cells, is elevated upon acquisition of tamoxifen resistance","authors":"Ningthoujam Sonia,&nbsp;Sreeja Mondal,&nbsp;Anil Mukund Limaye","doi":"10.1016/j.genrep.2025.102286","DOIUrl":"10.1016/j.genrep.2025.102286","url":null,"abstract":"<div><div>Matrix metalloproteinase-11 (MMP-11), also known as stromelysin-3, is a member of a large family of zinc-dependent proteinases. Known to be expressed in breast tumor stroma, the epithelium, and the associated mononuclear inflammatory cells, its expression is associated with invasion, metastasis, and poor clinical outcomes and survival rates. Despite the known effects of estrogen on extracellular matrix remodeling, and breast cancer metastasis, the role of MMP-11 therein is not understood. Here, we show that estrogen suppresses MMP-11 expression in MCF-7 breast cancer cells via a mechanism that involves binding of the estrogen receptor α (ERα) to an estrogen response element located in the intron-1 of MMP-11. ERα knockdown alone upregulates MMP-11 expression, highlighting its crucial role in this regulatory axis. Additionally, the anti-estrogen tamoxifen (4-OHT) blocks estrogen-mediated MMP-11 suppression. However, prolonged 4-OHT exposure or 4-OHT resistance leads to increased MMP-11 expression. This suggests that MMP-11 may play a role in 4-OHT resistance, potentially leading to a more aggressive tumor phenotype. Our study underscores the importance of estrogen-ERα signaling in breast cancer progression, emphasizing the need for further investigation into MMP-11's role in 4-OHT resistance and cancer metastasis.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"40 ","pages":"Article 102286"},"PeriodicalIF":1.0,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144595942","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":"Fatty acid metabolism heterogeneity in prostate cancer unveils prognostic biomarkers and immune crosstalk","authors":"Dan Yang ,&nbsp;Hanghang Chen ,&nbsp;Zhenqi Wang ,&nbsp;Haihua Luo,&nbsp;Yong Jiang","doi":"10.1016/j.genrep.2025.102280","DOIUrl":"10.1016/j.genrep.2025.102280","url":null,"abstract":"<div><h3>Background</h3><div>Fatty acid metabolism (FAM) is critical in prostate cancer (PCa), but few studies have explored its single-cell mechanisms. We analyzed single-cell and bulk transcriptome data from PCa patients to uncover FAM's role and identify potential therapeutic targets.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing identified ELOVL5, SCD, and FADS2 as key FAM genes. FAM scores were calculated using the “AUCell” algorithm and a gene list from the molecular signatures database. FAM scores in each cell type were compared between benign and cancerous samples. In three significant cell types, cells were grouped into high- and low-FAM categories based on median scores, and differentially expressed genes (DEGs) between groups were identified. DEGs were analyzed in bulk RNA sequencing to identify prognostic genes, validated by RT-qPCR. Cell interactions were explored using the “CellChat” algorithm to identify FAM-related communications.</div></div><div><h3>Results</h3><div>Three key FAM genes—ELOVL5, SCD, and FADS2—were differentially expressed between benign and cancerous samples. High FAM scores were observed in cancer cells and monocytes but lower in T cells. Cancer cells with high FAM scores showed increased stemness and copy number variations. In T cells and monocytes, FAM scores correlated with differentiation. CD226 and NECTIN2 were key interactions in the high-FAM group. Twelve FAM-related genes were identified as prognostic factors, validated by RT-qPCR.</div></div><div><h3>Conclusions</h3><div>FAM levels are elevated in prostate adenocarcinomas, particularly in cancer cells, monocytes, and T cells. High FAM scores correlate with stemness and genetic instability in cancer cells, while indicating increased differentiation in monocytes and T cells. CD226 and NECTIN2 were key interactions in the high-FAM group, suggesting FAM's role in NECTIN2–CD226 interactions and its potential link to the NECTIN2–TIGIT immune checkpoint axis.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"40 ","pages":"Article 102280"},"PeriodicalIF":1.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657256","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":"Role of activating transcription factor 3 in breast cancer progression: Tumor suppressor and oncogene perspectives","authors":"Dilipkumar Preetha,&nbsp;Iyyappan Saranya,&nbsp;Nagarajan Selvamurugan","doi":"10.1016/j.genrep.2025.102284","DOIUrl":"10.1016/j.genrep.2025.102284","url":null,"abstract":"<div><div>The adaptive response network uses activating transcription factor 3 (ATF3) as a central regulator, responding to stress signals. Basal levels of ATF3 expression maintain cellular homeostasis under normal physiological conditions. Various pathological conditions, including breast cancer, alter ATF3 expression through distinct regulatory mechanisms during disease progression. ATF3 acts as a tumor suppressor gene or an oncogene in a context-dependent manner. Particularly in breast cancer, ATF3 plays a multifaceted role by regulating cell proliferation, apoptosis, invasion, metastasis, and therapy resistance. The tumor microenvironment strongly influences ATF3 expression by modulating the immune landscape. Therefore, this review provides a brief overview of the influences on ATF3 expression and its interactions with key tumor-suppressive and oncogenic pathways in breast cancer. A more profound understanding of ATF3 and its role in breast cancer is crucial for the development of personalized therapeutic strategies to address the challenges posed by the heterogeneity of the disease.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"40 ","pages":"Article 102284"},"PeriodicalIF":1.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501639","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":"Unveiling the genetic symphony: Deep learning for decoding promoters and non-promoters in DNA sequence","authors":"Mohamudha Parveen Rahamathulla ,&nbsp;Shtwai Alsubai ,&nbsp;Mohemmed Sha","doi":"10.1016/j.genrep.2025.102283","DOIUrl":"10.1016/j.genrep.2025.102283","url":null,"abstract":"<div><div>Promoters are a significant area in the structure of DNA which is vital for the transcription of the exact gene in the genome. There are several types of promoters in the DNA that performs certain functions. The Mutations in the promoters are the major reason for many diseases like cancer, diabetes, etc. Effective identification of promoters is important for the diagnosis of certain diseases. The traditional identification of promoters is expensive and time-consuming. To resolve the issue, several conventional methods attempted to achieve better promoter and non-promoter identification systems but lack limitations like handling larger datasets, speed, and accuracy. Therefore, the projected system employs Bi-GRU (Bi-Gated Recurrent Units) with M-AM (Modified Attention Mechanism) to detect promoters and non-promoters in DNA sequence. Bi-GRU is utilized in the projected system for less complexity performance, better convergence speed, and the ability to work fast with huge data. Though it is widely utilized for detecting promoters and non-promoters, it has minor limitations, like handling larger datasets. To resolve this, the projected system utilizes Bi-GRU with M-AM to focus on the significant features of the data, which enhances the model's efficacy. M-AM of the numerical significances measure and sequence context weights. Promoters and non-promoters in the DNA sequence dataset are utilized in the projected system. Formerly, the performance of the projected system was calculated with evaluation metrics. Further, the proposed detection method is compared internally with LSTM (Long short-term Memory), BI-LSTM, and GRU to evaluate the model's efficiency. The projected detection of promoters and non-promoters is intended to assist researchers and physicians in genomics and molecular biology to enhance the diagnosis of the disease and disorders caused by the mutations of promoters.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"40 ","pages":"Article 102283"},"PeriodicalIF":1.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523183","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":"Full blood chimerism and de novo crossover at HLA in a phenotypically normal 46,XY woman","authors":"Caio Robledo D' Angioli Costa Quaio ,&nbsp;Margareth Afonso Torres ,&nbsp;Newton de Freitas Centurião ,&nbsp;Nair Hideko Muto ,&nbsp;Gustavo Arantes Rosa Maciel ,&nbsp;Patricia Karla de Souza ,&nbsp;Renata Kiyomi Kishimoto ,&nbsp;Mauren Fernanda Moller dos Santos ,&nbsp;Glaucia Santana Gomes ,&nbsp;Chong Ae Kim ,&nbsp;João Bosco de Oliveira Filho ,&nbsp;Elvira Deolinda R.P. Velloso","doi":"10.1016/j.genrep.2025.102282","DOIUrl":"10.1016/j.genrep.2025.102282","url":null,"abstract":"<div><h3>Background</h3><div>The finding of a 46,XY karyotype in a female is a rare phenomenon in humans and generally associated with conditions that cause some sort of gonadal impairment. We report the first case of complete blood chimerism combined with HLA recombination and mismatch between tissues in a phenotypically normal, fertile and healthy woman.</div></div><div><h3>Methods and Results</h3><div>Samples from blood, urine, buccal swab and skin biopsy from the female proband were analyzed through cytogenetic techniques, HLA typing and STR analysis and then the results were compared to her male twin brother in an attempt to clarify the etiology of her 46,XY karyotype. The proband has had a completely normal life with no remarkable health events and a normal sexual development; she had an early pregnancy loss following a spontaneous pregnancy at the age of 35. Karyotype in two repeated blood analyses resulted in 46,XY in all metaphases; FISH confirmed this pattern by showing one X and one Y signal in all 100 cells analyzed. Cytogenetic analyses of urine, buccal mucosa and skin fibroblasts resulted in 46,XX. STR profile and HLA genotyping of proband's blood was completely identical to her twin brother's, including the sexual markers, carrying a recombinant maternal HLA haplotype in HLA-A, E, and H loci created by a crossover, and divergent from her other tissue samples.</div></div><div><h3>Conclusions</h3><div>The presence of different cell populations present in different tissues suggests that the proband is a chimera. Blood chimerism, also known as twin chimerism or transfusion chimerism, is a rare phenomenon in humans and may manifest without any sexual anomalies or reproductive impact. The newly formed MHC haplotype demonstrates that immunogenetic reshuffling in newborns may lead to long-term tolerance, providing new insight into the immunobiology of natural chimeras.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"40 ","pages":"Article 102282"},"PeriodicalIF":1.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501624","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":"CXCR4 expression in colorectal cancer and tumor stage correlation","authors":"Fang Cao ,&nbsp;Yang Zhang ,&nbsp;Jianhao Xu ,&nbsp;Jiarui Min ,&nbsp;Jihao Su ,&nbsp;Zhe Chen ,&nbsp;Jingfeng Gu ,&nbsp;Zijie Xu ,&nbsp;Song Xu","doi":"10.1016/j.genrep.2025.102281","DOIUrl":"10.1016/j.genrep.2025.102281","url":null,"abstract":"<div><div>Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with incidence rates on the rise, particularly in developing countries such as China. This trend underscores the urgent need for novel molecular targets in cancer treatment. This study investigates the expression of C-X-C chemokine receptor type 4 (CXCR4) in CRC tissues compared to adjacent non-tumor tissues, evaluating its diagnostic potential and its relationship with tumor staging and clinical outcomes. Utilizing data from The Cancer Genome Atlas (TCGA) and clinical samples from 180 CRC patients, we conducted comprehensive analyses that included bioinformatics, immunohistochemistry, quantitative PCR, and Western blotting. Our results reveal that CXCR4 is significantly overexpressed in CRC tissues, with expression levels positively correlating with T stage and pTNM stage, as well as being associated with local tumor invasion and lymph node metastasis. However, we found no significant correlation between CXCR4 levels and overall or disease-free survival. The diagnostic utility of CXCR4 was further validated through receiver operating characteristic (ROC) curve analysis. These findings indicate that CXCR4 is markedly upregulated in CRC and correlates with tumor progression, suggesting it may have potential as a diagnostic and therapeutic target in colorectal cancer. However, further research is needed to evaluate its predictive power and applicability as a biomarker.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"40 ","pages":"Article 102281"},"PeriodicalIF":1.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517182","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":"Impact of hybridization on mitochondrial DNA in two kinds of hybrid groupers","authors":"Liu Cao ,&nbsp;Jun Ma ,&nbsp;Binbin Li ,&nbsp;Hanwen Fu ,&nbsp;Yan Lu ,&nbsp;Yatong Wu ,&nbsp;Pan Chen ,&nbsp;Xingrong Hou ,&nbsp;Ning Yang ,&nbsp;Hai Huang","doi":"10.1016/j.genrep.2025.102279","DOIUrl":"10.1016/j.genrep.2025.102279","url":null,"abstract":"<div><div>Animal mitochondrial DNA (mtDNA) follows the general rule of strict maternal inheritance. The event of hybridization could have an impact on the inherited pattern of mtDNA in hybrid. To investigate the impact of hybridization on mtDNA in different hybrid groupers, the mitogenomes of <em>Cromileptes altivelis</em> × <em>Epinephelus lanceolatus</em>(Hyb1), <em>E. fuscoguttatus</em> × <em>E. polyphekadion</em> (Hyb2), and their parents were determined using next-generation sequencing. Genetic diversity and haplotype network were also comparatively analyzed among two hybrid groupers based on the partial <em>cytochrome c oxidase 3 (cox3)</em>, <em>trnG</em> and <em>NADH dehydrogenase subunit 3</em> (<em>nad3</em>) sequences. Our results confirmed that mtDNA of two hybrid groupers were maternal inheritance, showing 99.8 % sequence similarity with their respective female parent. Their mitogenomes presented similar gene architectures. However, the different degrees of nucleotide variation have been detected in two hybrid groupers. Among these two hybrids, Hyb1 presented a higher level of genetic diversity compared with Hyb2. Our observations provide a significant knowledge to understand the effect of hybridization on mtDNA in hybrids.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"40 ","pages":"Article 102279"},"PeriodicalIF":1.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501638","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":"Hypoxia-related miRNA dysregulation in preeclampsia: The roles of miR-210 and miR-383","authors":"Nilgun Cekin ,&nbsp;Seyda Akin ,&nbsp;Irem Kucukyildiz ,&nbsp;Ergun Pinarbasi","doi":"10.1016/j.genrep.2025.102278","DOIUrl":"10.1016/j.genrep.2025.102278","url":null,"abstract":"<div><div>Insufficient placental blood perfusion is recognized as a contributing factor to preeclampsia (PE), resulting in persistent placental hypoxia. Under hypoxic conditions, certain microRNAs (miRNAs) exhibit varying expression levels. The literature suggests that miR-210 is integral to hypoxia response pathways, including angiogenesis, mitochondrial respiration, cell survival, and DNA repair. Conversely, miR-383 is believed to modulate the fundamental effects of hypoxia-inducible factor 1-alpha (HIF-1α) by targeting genes such as vascular endothelial growth factor and lactate dehydrogenase-A, which are regulated by HIF-1α in endothelial cells. This study aimed to evaluate miR-210 and miR-383 expression levels, anticipated to change under hypoxic conditions, using quantitative polymerase chain reaction (qPCR) in maternal blood (MB), placental tissue (PT), and umbilical cord blood (CB) samples from women with preeclampsia (PE) (<em>N</em> = 22) and control (<em>N</em> = 15). The study findings indicate that the expression of miR-210 increased, while the expression of miR-383 decreased in all samples from the PE group compared to the control group. In PE subgroups, miR-210 levels increased in MB by 3.78-fold and 2.73-fold, in PT by 3.67-fold and 2.49-fold, and in CB by 5.48-fold and 5.04-fold in the severe and mild PE groups, respectively (<em>p</em> &lt; 0.01). In contrast, a significant decrease in miR-383 expression was observed only in PT, with a 2.22-fold reduction (<em>p</em> = 0.01) in the severe PE group and a 7.69-fold reduction (<em>p</em> = 0.002) in the mild PE group. Evaluations comparing the severe and mild PE groups revealed significant differences in the expression of miR-210 in MB and PT, as well as miR-383 in PT (<em>p</em> = 0.01, <em>p</em> &lt; 0.001, and <em>p</em> = 0.001, respectively). According to the ANOVA test, miR-210 showed significant differences across all samples, while miR-383 showed significance only in PT (p &lt; 0.001). These findings suggest that miR-210 plays a key role in PE pathophysiology under hypoxic conditions, while miR-383 reduction, particularly in mild PE, may contribute to the condition's progression.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"40 ","pages":"Article 102278"},"PeriodicalIF":1.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470440","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":"Potential roles of hsa_circ_0003098 and hsa_circ_0013958 in pathophysiology of renal cell carcinoma","authors":"Hosein Mansoori ,&nbsp;Zahra Firoozi ,&nbsp;Elham Mohammadisoleimani ,&nbsp;Farshad Dehghani ,&nbsp;Masoomeh Rahpeima ,&nbsp;Mahsa Saffar ,&nbsp;Mohammad Mehdi Naghizadeh ,&nbsp;Ali Ariafar ,&nbsp;Shahryar Zeighami ,&nbsp;Yaser Mansoori","doi":"10.1016/j.genrep.2025.102275","DOIUrl":"10.1016/j.genrep.2025.102275","url":null,"abstract":"<div><h3>Background</h3><div>Renal cell carcinoma (RCC) is the predominant form of kidney cancer with certain subtypes carrying a relatively poor prognosis. Circular RNAs (circRNAs) have recently emerged as promising tools for early diagnosis of the more malignant subtypes in the context of competing endogenous RNA (ceRNA) networks.</div></div><div><h3>Materials and methods</h3><div>This is an experimental and in-silico study of the expression of hsa_circ_0003098 and hsa_circ_0013958 and their interaction with associated miRNAs and mRNAs in the context of tumor versus healthy tissues in RCC. The expression was assessed using qRT-PCR and ceRNA network was constructed using CircInteractome, miRTargetlink2, TargetScan, miRWallk, and STRING databases. GEPIA was employed for survival analysis and Cytoscape was used for network analysis. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the clinical and diagnostic value of hsa_circ_0003098 and hsa_circ_0013958.</div></div><div><h3>Results</h3><div>Both hsa_circ_0003098 and hsa_circ_0013958 were expressed at significantly lower levels in tumor tissues compared with normal tissues (<em>P</em>-value =0.013, &lt; 0.001). Interestingly, there was a significant association between the expression of hsa_circ_0013958 and kidney disease and tumor type. In silico analysis of the ceRNA network identified mRNAs and miRNAs crucial for RCC. Survival analysis of hub genes linked to each circRNA revealed several genes significantly impacting patient survival. Besides, hsa_circ_0003098 and hsa_circ_0013958 could act as diagnostic markers in RCC.</div></div><div><h3>Conclusion</h3><div>Our research showed that hsa_circ_0003098 and hsa_circ_0013958 were significantly downregulated in RCC tumors. This dysregulation of their miRNA/mRNA network affected important carcinogenic processes such as adhesion, migration, signaling, and cell cycle, which in turn provided insights into the molecular mechanisms of RCC.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"40 ","pages":"Article 102275"},"PeriodicalIF":1.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298535","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":"High expression of miR-145-3p associated with vascular and perineural invasion presence in cholangiocarcinoma","authors":"Pedro Henrique Fogaça Jordão ,&nbsp;Maria Clara Jéssica Calastri ,&nbsp;Rafael Fernandes-Ferreira ,&nbsp;Abner dos Santos Abreu ,&nbsp;Eliane Milharcix Zanovelo ,&nbsp;Larissa Bastos Eloy da Costa ,&nbsp;Rita de Cássia Martins Alves da Silva ,&nbsp;Ilka de Fátima Santana Ferreira Boin ,&nbsp;Dorotéia Rossi Silva Souza","doi":"10.1016/j.genrep.2025.102277","DOIUrl":"10.1016/j.genrep.2025.102277","url":null,"abstract":"<div><div>Cholangiocarcinoma (CCA) is a lethal malignancy of the bile ducts, where lymph node spread critically worsens survival and guides adjuvant chemotherapy decisions. Perineural and vascular invasions are linked to poor prognosis, with hypoxia driving vasculogenesis, angiogenesis, and metastasis. Vascular endothelial growth factor A (VEGFA) plays a key role in invasion and lymph node metastasis. It is regulated by microRNAs such as miR-145-3p and miR-101-3p, which can inhibit angiogenesis and influence EMT, cell migration, and metastasis. This study analyzed miR-145-3p, miR-101-3p, and <em>VEGFA</em> expression in CCA patients, focusing on their roles in invasion, differentiation, metastasis, and staging, alongside biological process enrichment for miR-145-3p target genes. A significant downregulation was observed for miR-145-3p, whereas miR-101-3p showed no changes. <em>VEGFA</em> was upregulated, underscoring its role in angiogenesis. Paradoxically, given its overall downregulation in CCA tissues, higher miR-145-3p levels were found in vascular and perineural invasion cases, suggesting interaction with the tumor microenvironment, possibly via TGF-β1. Elevated miR-145-3p expression in well-differentiated samples suggests it is a favorable prognostic marker and differentiation regulator. Biological enrichment analyses linked miR-145-3p targets to pathways driving vascular invasion, lymphangiogenesis, and TGF-β signaling. Perineural invasion involved nervous system development, MAPK signaling, axon guidance, and neurotrophin signaling, highlighting miR-145-3p's diverse roles in tumor progression and metastasis. Overall, our findings suggest that miR-145-3p acts as a multifaceted regulator in CCA, with potential as both a prognostic biomarker and therapeutic target. Future studies are warranted to elucidate its mechanistic contributions and clinical utility in guiding treatment strategies.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"40 ","pages":"Article 102277"},"PeriodicalIF":1.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335930","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}