Liang Jiangtao, Tang Jianming, Shi Huijuan, Li Hui, Zhen Tiantian, Duan Jing, Kang Lili, Zhang Fenfen, Dong Yu, Han Anjia
Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Oncotarget. 2017 Jul 26;8(47):82991-83008. doi: 10.18632/oncotarget.19635. eCollection 2017 Oct 10.
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.
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。