具核梭杆菌的FadA抗原：对结直肠癌和腺瘤性息肉进展中ceRNA网络的影响

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

作者信息

Rezasoltani Sama, Shams Elahe, Piroozkhah Moein, Aidi Yaser, Azizmohammad Looha Mehdi, Bagheri Parmida, Behzadi Andouhjerdi Roudabeh, Sadeghi Amir, Rejali Leili, Nazemalhosseini-Mojarad Ehsan

机构信息

Division of Oral Microbiology and Immunology, Department of Operative Dentistry, Periodontology and Preventive Dentistry, RWTH University Hospital, Aachen, Germany.

Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Discov Oncol. 2025 Jan 18;16(1):58. doi: 10.1007/s12672-025-01796-w.

DOI:10.1007/s12672-025-01796-w

PMID:39826054

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11741970/

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 (r = 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.

摘要

引言

结直肠癌（CRC）是全球癌症相关死亡的第二大常见原因。肠道微生物群与腺瘤性息肉（AP）一起，已成为CRC进展的一个可能因素。本研究旨在探讨具核梭杆菌衍生的FadA抗原对ANXA2 ceRNA网络表达水平的影响，并评估其与CRC进展的相关性。

材料与方法

ANXA2和LINC00460在CRC中的功能已部分阐明。根据我们之前鉴定ANXA2和LINC00460之间共享的微小RNA相互作用靶点（MIT）的研究，分别使用了TargetScanHuman（V7.2）和miRDB数据库。利用生物信息学和进化基因组学网络工具对共享微小RNA及其共同靶点进行交集分析。然后，构建ANXA2 ceRNA网络。随后，使用qRT-PCR检测30名健康对照、30名腺瘤患者和30例I期CRC患者的肠道活检标本中的mRNA、miRNA和lncRNA表达水平。

结果

与正常个体的样本相比，在CRC标本中观察到FadA、ANXA2、hsa-let-7a-2和LINC00460的表达水平升高，其次是AP病例。Spearman检验显示FadA与LINC00460之间存在强而显著的相关性（r = 0.9311，p < 0.0001）。此外，ANXA2的功能分析揭示了其通过JAK-STAT和Hippo信号通路对CRC进展的影响。