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线粒体基因组衍生的环状RNA SCAR/mc-COX2在结直肠癌中的病理表达及其ceRNA网络:对临床意义的启示

Pathological expression of mitochondrial genome-derived circRNA SCAR/mc-COX2 and its ceRNA network in colorectal cancer: implications for clinical significance.

作者信息

Nourbakhsh Seyed Taha, Mirzaei Seyed Abbas, Mohamadhashem Fatemeh, Naghizadeh Mohammad Mehdi, Razavi Amir Nader, Mansoori Yaser, Daraei Abdolreza, Mohamadhashem Faezeh

机构信息

Department of Medical Genetics, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Department of Medical Biotechnology, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.

出版信息

BMC Cancer. 2025 Mar 14;25(1):466. doi: 10.1186/s12885-025-13886-7.

Abstract

BACKGROUND

Mitochondrial-encoded circular RNAs (mecciRNAs) are a newly discovered class of mitochondrial-encoded non-coding RNAs (mt-ncRNAs) that play important biological roles in the cell. This study aimed to examine the expression profile of SCAR/mc-COX2 (has_circ_0089762) in colorectal cancer (CRC) and its relationship with clinicopathological variables. Furthermore, to better understand SCAR/mc-COX2's functional role in CRC, we constructed a competing endogenous RNA (ceRNA) network.

METHODS

Quantitative real-time PCR (qRT-PCR) was employed to analyze the expression levels of SCAR/mc-COX2 in 40 pairs of CRC samples, consisting of 40 tumor samples and 40 adjacent non-tumoral samples from patients. The ceRNA regulatory network was constructed using online bioinformatics tools. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) enrichment analysis were conducted using the Enrichr database.

RESULTS

The results demonstrated a significant decrease in SCAR/mc-COX2 expression in tumor tissues compared to adjacent non-tumoral tissues (p-value<0.05). In another finding, a significant relationship was observed between pathological T staging and the expression status of SCAR/mc-COX2 (p-value=0.02). Additionally, the Receiver Operating Characteristic (ROC) curve analysis revealed that SCAR/mc-COX2 had an area under the curve (AUC) of 0.77, with 80% sensitivity and 75% specificity. Finally, a ceRNA regulatory network including SCAR/mc-COX2, 5 miRNA, and 9 mRNAs was found.

CONCLUSION

These findings suggest that SCAR/mc-COX2 may act as a tumor suppressor in CRC, and its dysregulation could play a crucial role in the pathophysiology of this cancer. The significant association with pathological T staging and its robust diagnostic performance (AUC = 0.77, sensitivity = 80%, specificity = 75%) highlight its potential as a novel biomarker for CRC detection and prognosis. Further functional studies are required to elucidate its precise role in CRC tumorigenesis and clinical applicability.

摘要

背景

线粒体编码的环状RNA(mecciRNAs)是一类新发现的线粒体编码的非编码RNA(mt-ncRNAs),在细胞中发挥重要的生物学作用。本研究旨在检测SCAR/mc-COX2(has_circ_0089762)在结直肠癌(CRC)中的表达谱及其与临床病理变量的关系。此外,为了更好地理解SCAR/mc-COX2在CRC中的功能作用,我们构建了一个竞争性内源性RNA(ceRNA)网络。

方法

采用定量实时PCR(qRT-PCR)分析40对CRC样本中SCAR/mc-COX2的表达水平,这些样本包括40例肿瘤样本和来自患者的40例相邻非肿瘤样本。使用在线生物信息学工具构建ceRNA调控网络。此外,使用Enrichr数据库进行京都基因与基因组百科全书(KEGG)通路分析和基因本体(GO)富集分析。

结果

结果表明,与相邻非肿瘤组织相比,肿瘤组织中SCAR/mc-COX2的表达显著降低(p值<0.05)。另一项发现是,病理T分期与SCAR/mc-COX2的表达状态之间存在显著关系(p值=0.02)。此外,受试者工作特征(ROC)曲线分析显示,SCAR/mc-COX2的曲线下面积(AUC)为0.77,灵敏度为80%,特异性为75%。最后,发现了一个包括SCAR/mc-COX2、5种miRNA和9种mRNA的ceRNA调控网络。

结论

这些发现表明,SCAR/mc-COX2可能在CRC中作为肿瘤抑制因子发挥作用,其失调可能在该癌症的病理生理学中起关键作用。与病理T分期的显著关联及其强大的诊断性能(AUC = 0.77,灵敏度 = 80%,特异性 = 75%)突出了其作为CRC检测和预后新生物标志物的潜力。需要进一步的功能研究来阐明其在CRC肿瘤发生中的精确作用和临床适用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba4/11907809/b46cbb045229/12885_2025_13886_Fig1_HTML.jpg

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