MiR-532-3p suppresses colorectal cancer progression by disrupting the ETS1/TGM2 axis-mediated Wnt/β-catenin signaling
MiR-532-3p suppresses colorectal cancer progression by disrupting the ETS1/TGM2 axis-mediated Wnt/β-catenin signaling
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MiR-532-3p 通过破坏 ETS1/TGM2 轴介导的 Wnt/β-连环蛋白信号传导来抑制结直肠癌进展
DOI：
10.1038/s41419-019-1962-x
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发表时间：
2019-09-30
影响因子：
9
通讯作者：
Liu, Side
中科院分区：
文献类型：
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作者：
Gu, Chuncai;Cai, Jianqun;Liu, Side
血浆 microRNA 的表达组将 miR-532-3p 定义为结直肠腺瘤 (CRA) 的有价值的生物标志物。然而，其在结直肠癌（CRC）中的表达模式和功能仍不清楚。本研究调查了 miR-532-3p 的表达水平，发现它在 CRA 和 CRC 中原位下调。此外，它通过激活 p53 和细胞凋亡信号通路，诱导细胞周期停滞和早期细胞凋亡，从而充当 CRC 化疗的增敏剂。此外，还发现 miR-532-3p 可以抑制 CRC 的细胞生长、转移和上皮间质转化 (EMT) 表型。对这些效应背后机制的研究表明，miR-532-3p 直接结合 ETS1 和 TGM2 的 3'UTR 区域，最终抑制经典的 Wnt/β-catenin 信号传导。进一步研究表明，TGM2 受 ETS1 转录调控，ETS1/TGM2 轴是 miR-532-3p 抑制 CRC 进展的重要功能靶点。总之，miR-532-3p 模拟物可以通过灭活经典 Wnt/β-catenin 信号传导和增强化疗敏感性，作为 CRC 分子治疗的潜在候选者。
The expression panel of plasma microRNA defined miR-532-3p as a valuable biomarker for colorectal adenoma (CRA). However, its expression pattern and function in colorectal cancer (CRC) have remained unclear. The present study investigated the expression levels of miR-532-3p and found that it was in situ downregulated both in CRA and CRC. Moreover, it functioned as a sensitizer for chemotherapy in CRC by inducing cell cycle arrest and early apoptosis via its activating effects on p53 and apoptotic signaling pathways. In addition, miR-532-3p was found to restrain cell growth, metastasis, and epithelial–mesenchymal transition (EMT) phenotype of CRC. A study on the mechanism behind these effects revealed that miR-532-3p directly binds to 3′UTR regions of ETS1 and TGM2, ultimately repressing the canonical Wnt/β-catenin signaling. Further investigation showed that TGM2 was transcriptionally regulated by ETS1 and ETS1/TGM2 axis served as a vital functional target of miR-532-3p in suppressing CRC progression. To conclude, miR-532-3p mimics could act as potential candidate for molecular therapy in CRC through inactivation of the canonical Wnt/β-catenin signaling and enhancement of chemosensitivity.