FadA antigen of Fusobacterium nucleatum: implications for ceRNA network in colorectal cancer and adenomatous polyps progression

Abstract Introduction Colorectal cancer (CRC) is the second most common cause of cancer-related deaths globally. The gut microbiota, along with adenomatous polyps (AP), has emerged as a plausible contributor to CRC progression. This study aimed to scrutinize the impact of the FadA antigen derived fr...

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Main Authors: Sama Rezasoltani, Elahe Shams, Moein Piroozkhah, Yaser Aidi, Mehdi Azizmohammad Looha, Parmida Bagheri, Roudabeh Behzadi Andouhjerdi, Amir Sadeghi, Leili Rejali, Ehsan Nazemalhosseini-Mojarad
Format: Article
Language:English
Published: Springer 2025-01-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-01796-w
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author Sama Rezasoltani
Elahe Shams
Moein Piroozkhah
Yaser Aidi
Mehdi Azizmohammad Looha
Parmida Bagheri
Roudabeh Behzadi Andouhjerdi
Amir Sadeghi
Leili Rejali
Ehsan Nazemalhosseini-Mojarad
author_facet Sama Rezasoltani
Elahe Shams
Moein Piroozkhah
Yaser Aidi
Mehdi Azizmohammad Looha
Parmida Bagheri
Roudabeh Behzadi Andouhjerdi
Amir Sadeghi
Leili Rejali
Ehsan Nazemalhosseini-Mojarad
author_sort Sama Rezasoltani
collection DOAJ
description Abstract Introduction Colorectal cancer (CRC) is the second most common cause of cancer-related deaths globally. The gut microbiota, along with adenomatous polyps (AP), has emerged as a plausible contributor to CRC progression. This study aimed to scrutinize the impact of the FadA antigen derived from Fusobacterium nucleatum on the expression levels of the ANXA2 ceRNA network and assess its relevance to CRC advancement. Material and methods The functions of ANXA2 and LINC00460 in CRC have been partially clarified. According to our previous study to identify shared MicroRNA-Interaction-Targets (MITs) between ANXA2 and LINC00460, TargetScanHuman (V7.2) and miRDB databases have been used respectively. The Bioinformatics and Evolutionary Genomics web tool was employed to intersect the sets of shared microRNAs and their common targets. Then, the ANXA2 ceRNA network was constructed. Subsequently, the mRNA, miRNA, and lncRNA expression levels were examined in intestinal biopsy specimens from 30 healthy controls, 30 Adenoma patients, and 30 cases of CRC stage I using qRT-PCR. Results Elevated expression levels of FadA, ANXA2, hsa-let-7a-2, and LINC00460 were observed in CRC specimens, followed by AP cases, in comparison to samples from normal individuals. Application of the Spearman test revealed a strong and significant correlation between FadA and LINC00460 (rS = 0.9311, p < 0.0001). Also, the functional analysis of ANXA2 revealed its impact on CRC progression through JAK-STAT and Hippo signaling pathways. Conclusion FadA appears to potentiate CRC progression by inducing the upregulation of LINC00460, consequently leading to the hyperexpression of ANXA2 through the ceRNA network.
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spelling doaj-art-ce8f2d59b86e4d6892be29342e2a37ed2025-01-19T12:29:14ZengSpringerDiscover Oncology2730-60112025-01-0116111410.1007/s12672-025-01796-wFadA antigen of Fusobacterium nucleatum: implications for ceRNA network in colorectal cancer and adenomatous polyps progressionSama Rezasoltani0Elahe Shams1Moein Piroozkhah2Yaser Aidi3Mehdi Azizmohammad Looha4Parmida Bagheri5Roudabeh Behzadi Andouhjerdi6Amir Sadeghi7Leili Rejali8Ehsan Nazemalhosseini-Mojarad9Division of Oral Microbiology and Immunology, Department of Operative Dentistry, Periodontology and Preventive Dentistry, RWTH University HospitalBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesDepartment of Genetics, Islamic Azad University of Central Tehran BranchBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesDepartment of Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti UniversityDepartment of Genetics, Islamic Azad University of Central Tehran BranchGastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesGastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesAbstract Introduction Colorectal cancer (CRC) is the second most common cause of cancer-related deaths globally. The gut microbiota, along with adenomatous polyps (AP), has emerged as a plausible contributor to CRC progression. This study aimed to scrutinize the impact of the FadA antigen derived from Fusobacterium nucleatum on the expression levels of the ANXA2 ceRNA network and assess its relevance to CRC advancement. Material and methods The functions of ANXA2 and LINC00460 in CRC have been partially clarified. According to our previous study to identify shared MicroRNA-Interaction-Targets (MITs) between ANXA2 and LINC00460, TargetScanHuman (V7.2) and miRDB databases have been used respectively. The Bioinformatics and Evolutionary Genomics web tool was employed to intersect the sets of shared microRNAs and their common targets. Then, the ANXA2 ceRNA network was constructed. Subsequently, the mRNA, miRNA, and lncRNA expression levels were examined in intestinal biopsy specimens from 30 healthy controls, 30 Adenoma patients, and 30 cases of CRC stage I using qRT-PCR. Results Elevated expression levels of FadA, ANXA2, hsa-let-7a-2, and LINC00460 were observed in CRC specimens, followed by AP cases, in comparison to samples from normal individuals. Application of the Spearman test revealed a strong and significant correlation between FadA and LINC00460 (rS = 0.9311, p < 0.0001). Also, the functional analysis of ANXA2 revealed its impact on CRC progression through JAK-STAT and Hippo signaling pathways. Conclusion FadA appears to potentiate CRC progression by inducing the upregulation of LINC00460, consequently leading to the hyperexpression of ANXA2 through the ceRNA network.https://doi.org/10.1007/s12672-025-01796-wColorectal cancerAdenoma polypsFusobacterium nucleatumFadAceRNA networkANXA2
spellingShingle Sama Rezasoltani
Elahe Shams
Moein Piroozkhah
Yaser Aidi
Mehdi Azizmohammad Looha
Parmida Bagheri
Roudabeh Behzadi Andouhjerdi
Amir Sadeghi
Leili Rejali
Ehsan Nazemalhosseini-Mojarad
FadA antigen of Fusobacterium nucleatum: implications for ceRNA network in colorectal cancer and adenomatous polyps progression
Discover Oncology
Colorectal cancer
Adenoma polyps
Fusobacterium nucleatum
FadA
ceRNA network
ANXA2
title FadA antigen of Fusobacterium nucleatum: implications for ceRNA network in colorectal cancer and adenomatous polyps progression
title_full FadA antigen of Fusobacterium nucleatum: implications for ceRNA network in colorectal cancer and adenomatous polyps progression
title_fullStr FadA antigen of Fusobacterium nucleatum: implications for ceRNA network in colorectal cancer and adenomatous polyps progression
title_full_unstemmed FadA antigen of Fusobacterium nucleatum: implications for ceRNA network in colorectal cancer and adenomatous polyps progression
title_short FadA antigen of Fusobacterium nucleatum: implications for ceRNA network in colorectal cancer and adenomatous polyps progression
title_sort fada antigen of fusobacterium nucleatum implications for cerna network in colorectal cancer and adenomatous polyps progression
topic Colorectal cancer
Adenoma polyps
Fusobacterium nucleatum
FadA
ceRNA network
ANXA2
url https://doi.org/10.1007/s12672-025-01796-w
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