与左、右侧结直肠癌生物学通路相关的 microRNAs。

MicroRNAs Associated With Biological Pathways of Left- and Right-sided Colorectal Cancer.

机构信息

School of Medicine, Institute of Clinical Medicine, Clinical Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.

Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland.

出版信息

Anticancer Res. 2020 Jul;40(7):3713-3722. doi: 10.21873/anticanres.14360.

DOI:10.21873/anticanres.14360

PMID:32620610

Abstract

BACKGROUND/AIM: MicroRNAs (miRNAs) regulate the development of colorectal cancer (CRC). We aimed to investigate miRNAs and their relation to cancer-related signaling pathways in site-specific CRC.

MATERIALS AND METHODS

We used a total of 24 left- and right-sided Finnish CRC samples (discovery cohort) and The Cancer Genome Atlas public mature miRSeq dataset of 201 CRC samples (validation cohort). MiRNA differential expression and biological pathway analyses were performed using DESeq2 and the DIANA/mirPath tool, respectively.

RESULTS

We found 17 significantly differentially up-regulated [false discovery rate (FDR) <0.05] miRNAs in left-sided CRC ("left miRNAs"), and 15 in right-sided CRC ("right miRNAs"). The left miRNAs participate in the mTor, Wnt, PI3K-Akt signaling pathways (FDR<0.05). The right miRNAs participate in the TGF-β signaling pathway. We also observed that both cohorts share six miRNAs. One of these (hsa-miR-196b-5p) was significantly (FDR<0.05) up-regulated in left-sided CRC. The rest of them (hsa-miR-625-3p, hsa-miR-155-5p, hsa-miR-625-5p, hsa-miR-31-5p and hsa-miR-330-5p) showed significant (FDR<0.05) up-regulation in right-sided CRC.

CONCLUSION

Left and right miRNAs are associated with predominant biological pathways of left- and right-sided CRC, respectively. Our results may be beneficial for classifying CRC and for future biomarker studies of site-specific CRC.

摘要

背景/目的：微小 RNA（miRNA）调节结直肠癌（CRC）的发展。我们旨在研究特定部位 CRC 中的 miRNA 及其与癌症相关信号通路的关系。

材料和方法

我们使用了总共 24 个芬兰左、右侧 CRC 样本（发现队列）和 201 个 CRC 样本的癌症基因组图谱公共成熟 miRSeq 数据集（验证队列）。使用 DESeq2 和 DIANA/mirPath 工具分别进行 miRNA 差异表达和生物途径分析。

结果

我们在左侧 CRC 中发现了 17 个显著上调的差异表达 miRNA（错误发现率（FDR）<0.05），在右侧 CRC 中发现了 15 个差异表达 miRNA。左侧 miRNA 参与 mTor、Wnt、PI3K-Akt 信号通路（FDR<0.05）。右侧 miRNA 参与 TGF-β 信号通路。我们还观察到两个队列共有的 6 个 miRNA。其中之一（hsa-miR-196b-5p）在左侧 CRC 中显著上调（FDR<0.05）。其余的（hsa-miR-625-3p、hsa-miR-155-5p、hsa-miR-625-5p、hsa-miR-31-5p 和 hsa-miR-330-5p）在右侧 CRC 中也表现出显著上调（FDR<0.05）。