miR-27a-3p targeting RXRα promotes colorectal cancer progression by activating Wnt/β-catenin pathway.
miR-27a-3p targeting RXRα promotes colorectal cancer progression by activating Wnt/β-catenin pathway.
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靶向 RXR α 的 miR-27a-3p 通过激活 Wnt/β-catenin 通路促进结直肠癌进展
DOI：
10.18632/oncotarget.19635
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发表时间：
2017-10-10
期刊：
影响因子：
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通讯作者：
Han A
中科院分区：
文献类型：
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作者：
Liang J;Tang J;Shi H;Li H;Zhen T;Duan J;Kang L;Zhang F;Dong Y;Han A
本研究旨在阐明miR-27A-3p如何调节Wnt/β-catenin信号通路促进结直肠癌的进展。结果表明，miR-27A-3p在结直肠癌组织中表达上调，并与组织分化程度、临床分期、远处转移及患者的生存密切相关。在体内外，miR-27A-3p模拟抑制大肠癌细胞的凋亡，促进其增殖、迁移、侵袭。而miR-27A-3p抑制剂在体内外均能促进肿瘤细胞的凋亡，抑制细胞的增殖、迁移和侵袭。此外，rxrα是miR-27A-3p基因在结直肠癌中的靶基因。结直肠癌组织中MIR-27A-3p的表达与RXRα的表达呈负相关。机制研究表明，miR-27A-3p/RXR、α/Wnt/β-catenin信号通路参与了结直肠癌的发生发展。综上所述，我们的研究结果首次证明miR-27A-3p是结直肠癌患者预后和/或潜在治疗的生物标志物，而RXRα作为miR-27A-3p靶向基因在结直肠癌进展过程中Wnt/β-catenin通路的激活中起着重要作用。
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 in vitro and in vivo. Whereas miR-27a-3p inhibitor promoted apoptosis and suppressed proliferation, migration, invasion of CRC cells in vitro and in vivo. 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.