Objective

MicroRNAs (miRNAs) have been demonstrated to be differently expressed in colorectal cancer (CRC) and were identified as biomarkers and therapeutic targets for CRC. We aimed to identify the effect of microRNA-424 (miR-424) on process of CRC.

Methods

Exosomes were obtained from bone marrow mesenchymal stem cells (BMSCs). MiR-424, transforming growth factor-β receptor 3 (TGFBR3) vimentin, S100A4, p-Smad1 expression in tissues and cells was measured. After treated with miR-424 inhibitor or TGFBR3 overexpression plasmid, the migration, invasion, cell cycle distribution and apoptosis of Lovo cells and exosomes-transfected Lovo cells were determined. The subcutaneous tumor models were established and the tumor growth was observed. The target relation between miR-424 and TGFBR3 was confirmed.

Results

MiR-424 was upregulated while TGFBR3 was downregulated in CRC tissues. TGFBR3 was targeted by miR-424. Inhibited miR-424 or elevated TGFBR3 upregulated p-Smad1, indicating that TGFBR3 mediated the Smad1 pathway, thus regulating CRC progression. MiR-424 inhibition or TGFBR3 restoration also suppressed migration and invasion of CRC cells, arrested the CRC cells at G0/G1 phase, and promoted CRC cell apoptosis. Moreover, exosomal miR-424 from BMSCs promoted CRC development.

Conclusion

Inhibited exosomal miR-424 from BMSCs inhibited malignant behaviors of CRC cells by targeting TGFBR3, thus suppressing the progression of CRC.

中文翻译：

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撤回：抑制骨髓间充质干细胞来源的外泌体中的 microRNA-424 通过上调 TGFBR3 抑制结直肠癌的肿瘤生长

 客观的

MicroRNA (miRNA) 已被证明在结直肠癌 (CRC) 中存在不同表达，并被确定为 CRC 的生物标志物和治疗靶点。我们的目的是确定 microRNA-424 (miR-424) 对 CRC 过程的影响。

 方法

外泌体是从骨髓间充质干细胞（BMSC）中获得的。测量组织和细胞中miR-424、转化生长因子-β受体3（TGFBR3）波形蛋白、S100A4、p-Smad1的表达。用miR-424抑制剂或TGFBR3过表达质粒处理后，测定Lovo细胞和外泌体转染的Lovo细胞的迁移、侵袭、细胞周期分布和凋亡。建立皮下肿瘤模型并观察肿瘤生长情况。证实了miR-424和TGFBR3之间的靶关系。

 结果

在 CRC 组织中，miR-424 上调，而 TGFBR3 下调。 TGFBR3 是 miR-424 的靶标。抑制 miR-424 或升高 TGFBR3 上调 p-Smad1，表明 TGFBR3 介导 Smad1 通路，从而调节 CRC 进展。抑制miR-424或恢复TGFBR3还可以抑制CRC细胞的迁移和侵袭，将CRC细胞阻滞在G0/G1期，并促进CRC细胞凋亡。此外，来自 BMSC 的外泌体 miR-424 促进了 CRC 的发展。

 结论

抑制来自 BMSC 的外泌体 miR-424 通过靶向 TGFBR3 抑制 CRC 细胞的恶性行为，从而抑制 CRC 的进展。