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外泌体miR-193a和let-7g促进原发性结直肠癌及配对的腹膜转移癌的癌症进展。

Exosomal miR-193a and let-7g accelerate cancer progression on primary colorectal cancer and paired peritoneal metastatic cancer.

作者信息

Cho Woo-Cheol, Kim Minjung, Park Ji Won, Jeong Seung-Yong, Ku Ja-Lok

机构信息

Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea; Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; Cancer Research Institute, Seoul National University, Seoul 03080, Republic of Korea.

Cancer Research Institute, Seoul National University, Seoul 03080, Republic of Korea; Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Korea; Division of Colorectal Surgery, Department of Surgery, Seoul National University Hospital, Seoul 03080, Korea.

出版信息

Transl Oncol. 2021 Feb;14(2):101000. doi: 10.1016/j.tranon.2020.101000. Epub 2020 Dec 20.

Abstract

A metastasis of colorectal cancer is difficult to diagnose, and has a poor prognosis. Therefore, we tried to elucidate the possibility of a diagnostic and prognostic marker. Exosomal miR-193a and let-7g were sorted by miRNA microarray. The expression of miR-193a in the PTM group was lower than that of the primary CRC group, and the expression of let-7g was higher than that of the primary CRC. MMP16 and CDKN1A expression was confirmed respectively for target genes of two miRNAs. When the mimics of these miRNAs were treated with cell lines, both MMP16 and CDKN1A decreased intracellular expression. Cell invasiveness and proliferation were decreased by miR-193a and increased by let-7g. The differences in expression of exosomal miR-193a and let-7g extracted from the plasma of patients were classified as cancer progression indicators. Furthermore, the survival rate decreased in the group with low miR-193a expression and high let-7g expression. Our study confirmed the possibility of using this as a diagnostic and prognostic marker for colorectal cancer by measuring the expression levels of exosomal miR-193a and let-7g in blood.

摘要

结直肠癌转移难以诊断,且预后较差。因此,我们试图阐明一种诊断和预后标志物的可能性。通过miRNA微阵列分选外泌体miR-193a和let-7g。PTM组中miR-193a的表达低于原发性结直肠癌组,而let-7g的表达高于原发性结直肠癌组。分别针对两种miRNA的靶基因证实了MMP16和CDKN1A的表达。当用这些miRNA的模拟物处理细胞系时,MMP16和CDKN1A的细胞内表达均降低。miR-193a降低细胞侵袭性和增殖,而let-7g则增加细胞侵袭性和增殖。从患者血浆中提取的外泌体miR-193a和let-7g的表达差异被归类为癌症进展指标。此外,miR-193a表达低且let-7g表达高的组生存率降低。我们的研究证实了通过测量血液中外泌体miR-193a和let-7g的表达水平,将其用作结直肠癌诊断和预后标志物的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/627f/7758376/d66fcb53e7b9/gr1.jpg

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