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靶向RXRα的miR-27a-3p通过激活Wnt/β-连环蛋白通路促进结直肠癌进展。

miR-27a-3p targeting RXRα promotes colorectal cancer progression by activating Wnt/β-catenin pathway.

作者信息

Liang Jiangtao, Tang Jianming, Shi Huijuan, Li Hui, Zhen Tiantian, Duan Jing, Kang Lili, Zhang Fenfen, Dong Yu, Han Anjia

机构信息

Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

出版信息

Oncotarget. 2017 Jul 26;8(47):82991-83008. doi: 10.18632/oncotarget.19635. eCollection 2017 Oct 10.

Abstract

This study aimed to elucidate how miR-27a-3p modulates the Wnt/β-catenin signaling pathway to promote colorectal cancer (CRC) progression. Our results showed that the expression of miR-27a-3p was up-regulated in CRC and closely associated with histological differentiation, clinical stage, distant metastasis and CRC patients' survival. miR-27a-3p mimic suppressed apoptosis and promoted proliferation, migration, invasion of CRC cells and . Whereas miR-27a-3p inhibitor promoted apoptosis and suppressed proliferation, migration, invasion of CRC cells and . Furthermore, RXRα was the target gene of miR-27a-3p in CRC. miR-27a-3p expression negatively correlated with RXRα expression in CRC tissues. The underlining mechanism study showed that miR-27a-3p/RXRα/Wnt/β-catenin signaling pathway is involved in CRC progression. In conclusion, our findings first demonstrate that miR-27a-3p is a prognostic and/or potential therapeutic biomarker for CRC patients and RXRα as miR-27a-3p targeting gene plays an important role in activation of the Wnt/β-catenin pathway during CRC progression.

摘要

本研究旨在阐明miR-27a-3p如何调节Wnt/β-连环蛋白信号通路以促进结直肠癌(CRC)进展。我们的结果表明,miR-27a-3p在CRC中表达上调,且与组织学分化、临床分期、远处转移及CRC患者的生存率密切相关。miR-27a-3p模拟物抑制CRC细胞凋亡并促进其增殖、迁移和侵袭。而miR-27a-3p抑制剂则促进CRC细胞凋亡并抑制其增殖、迁移和侵袭。此外,RXRα是CRC中miR-27a-3p的靶基因。在CRC组织中,miR-27a-3p表达与RXRα表达呈负相关。进一步的机制研究表明,miR-27a-3p/RXRα/Wnt/β-连环蛋白信号通路参与了CRC进展。总之,我们的研究结果首次表明,miR-27a-3p是CRC患者的一个预后和/或潜在治疗生物标志物,而作为miR-27a-3p靶向基因的RXRα在CRC进展过程中Wnt/β-连环蛋白通路的激活中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfe3/5669944/56c4b86a1d40/oncotarget-08-82991-g001.jpg

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