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miR-486-5p在结直肠癌肿瘤干细胞表型中的作用

The Role of miR-486-5p on CSCs Phenotypes in Colorectal Cancer.

作者信息

Etzi Federica, Griñán-Lisón Carmen, Fenu Grazia, González-Titos Aitor, Pisano Andrea, Farace Cristiano, Sabalic Angela, Picon-Ruiz Manuel, Marchal Juan Antonio, Madeddu Roberto

机构信息

Department of Biomedical Science, University of Sassari, 07100 Sassari, Italy.

Department of Biochemistry and Molecular Biology 2, Faculty of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.

出版信息

Cancers (Basel). 2024 Dec 19;16(24):4237. doi: 10.3390/cancers16244237.

Abstract

BACKGROUND

Colorectal cancer (CRC) is the third diagnosed cancer worldwide. Forty-four percent of metastatic colorectal cancer patients were diagnosed at an early stage. Despite curative resection, approximately 40% of patients will develop metastases within a few years. Previous studies indicate the presence of cancer stem cells (CSCs) and their contribution to CRC progression and metastasis. miRNAs deregulation plays a role in CSCs formation and in tumor development. In light of previous studies, we investigated the role of miR-486-5p to understand its role in CSC better.

METHODS

The expression of miR-486-5p was assessed in adherent cells and spheres generated from two CRC cell lines to observe the difference in expression in CSC-enriched spheroids. Afterward, we overexpressed and underexpressed this miRNA in adherent and sphere cultures through the transfection of a miR-486-5p mimic and a mimic inhibitor.

RESULTS

The results demonstrated that miR-486-5p exhibited a notable downregulation in CSC models, and its overexpression led to a significant decrease in colony size.

CONCLUSIONS

In this study, we confirmed that miR-486-5p plays an oncosuppressive role in CRC, thereby advancing our understanding of the role of this microRNA in the CSC phenotype.

摘要

背景

结直肠癌(CRC)是全球第三大确诊癌症。44%的转移性结直肠癌患者在早期被诊断出来。尽管进行了根治性切除,但仍有大约40%的患者会在几年内发生转移。先前的研究表明癌症干细胞(CSCs)的存在及其对CRC进展和转移的作用。miRNAs失调在CSCs形成和肿瘤发展中起作用。鉴于先前的研究,我们研究了miR-486-5p的作用,以更好地了解其在CSC中的作用。

方法

评估miR-486-5p在两种CRC细胞系产生的贴壁细胞和球体中的表达,以观察富含CSC的球体中表达的差异。之后,我们通过转染miR-486-5p模拟物和模拟抑制剂,在贴壁和球体培养物中过表达和低表达这种miRNA。

结果

结果表明,miR-486-5p在CSC模型中表现出显著下调,其过表达导致集落大小显著减小。

结论

在本研究中,我们证实miR-486-5p在CRC中发挥肿瘤抑制作用,从而增进了我们对这种microRNA在CSC表型中作用的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5011/11674241/e29b54f7296c/cancers-16-04237-g001a.jpg

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