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微小RNA-146a通过羧肽酶M/源黏着斑激酶途径促进人结直肠癌细胞的迁移和侵袭。

MicroRNA-146a promote cell migration and invasion in human colorectal cancer via carboxypeptidase M/src-FAK pathway.

作者信息

Lu Di, Yao Qunyan, Zhan Cheng, Le-Meng Zhang, Liu Hongchun, Cai Yu, Tu Chuantao, Li Xi, Zou Yanting, Zhang Shuncai

机构信息

Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

出版信息

Oncotarget. 2017 Apr 4;8(14):22674-22684. doi: 10.18632/oncotarget.15158.

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide, and microRNAs play important roles in CRC progression. This study aimed to investigate the roles of miR-146a-5p in human CRC and their molecular mechanisms. First, we found that miR-146a-5p was significantly upregulated in CRC tissues and promoted the migration of CRC cells. Then, we identified carboxypeptidase M (CPM) as a direct target of miR-146a-5p, and found that it inhibited the migration and invasion of CRC cells. Our results also showed that CPM expression was positively correlated with overall survival and negatively correlated with recurrence, lymph node invasion, and N stage. Furthermore, we demonstrated that both miR-146a-5p and CPM regulated Src and FAK expression, while the Src-FAK signaling pathway is widely known to be associated with the migration and invasion of multiple tumor cells. This study is the first to demonstrate the functional and mechanistic relationship of the miR-146a-5p/CPM/Src-FAK axis and its effect on the migration and invasion of CRC cells. Thus, miR-146a-5p represents potential targets for CRC diagnosis and therapy.

摘要

结直肠癌(CRC)是全球最常见的癌症之一,微小RNA在CRC进展中发挥重要作用。本研究旨在探讨miR-146a-5p在人CRC中的作用及其分子机制。首先,我们发现miR-146a-5p在CRC组织中显著上调,并促进CRC细胞的迁移。然后,我们鉴定出羧肽酶M(CPM)是miR-146a-5p的直接靶标,并发现它抑制CRC细胞的迁移和侵袭。我们的结果还表明,CPM表达与总生存期呈正相关,与复发、淋巴结侵袭和N分期呈负相关。此外,我们证明miR-146a-5p和CPM均调节Src和FAK表达,而Src-FAK信号通路众所周知与多种肿瘤细胞的迁移和侵袭有关。本研究首次证明了miR-146a-5p/CPM/Src-FAK轴的功能和机制关系及其对CRC细胞迁移和侵袭的影响。因此,miR-146a-5p代表了CRC诊断和治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6b/5410254/91b251c1e711/oncotarget-08-22674-g001.jpg

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