MicroRNA-140, a cartilage-specific microRNA, has recently been implicated in the cancer progression. However, the comprehensive role of miR-140 in the invasion and metastasis of colorectal cancer (CRC) is still not fully understood. In this study, we confirmed that miR-140 downregulates SMAD family member 3 (Smad3), which is a key downstream effector of the TGF-β signaling pathway, at the translational level in the CRC cell lines. Ectopic expression of miR-140 inhibits the process of epithelial-mesenchymal transition (EMT), at least partially through targeting Smad3, and induces the suppression of migratory and invasive capacities of CRC cells in vitro. miR-140 also attenuates CRC cell proliferation possibly via downregulating Samd3. Furthermore, overexpression of miR-140 inhibits the tumor formation and metastasis of CRC in vivo, and silenced Smad3 has the similar effect. Additionally, miR-140 expression is decreased in the clinical primary CRC specimens and appears as a progressive reduction in the metastatic specimens, whereas Smad3 is overexpressed in the CRC samples. Taken together, our findings suggest that miR-140 might be a key suppressor of CRC progression and metastasis through inhibiting EMT process by targeting Smad3. miR-140 may represent a novel candidate for CRC treatment.

MicroRNA-140 是一种软骨特异性 microRNA，最近与癌症进展有关。然而，miR-140在结直肠癌（CRC）侵袭转移中的综合作用仍未完全了解。在这项研究中，我们证实 miR-140 在 CRC 细胞系的翻译水平下调 SMAD 家族成员 3 (Smad3)，这是 TGF-β 信号通路的关键下游效应子。miR-140 的异位表达至少部分通过靶向 Smad3 抑制上皮-间质转化 (EMT) 过程，并在体外抑制 CRC 细胞的迁移和侵袭能力. miR-140 还可能通过下调 Samd3 来减弱 CRC 细胞增殖。此外，miR-140的过表达在体内抑制了CRC的肿瘤形成和转移，沉默的Smad3具有类似的作用。此外，miR-140 表达在临床原发性 CRC 标本中减少，并表现为转移标本中的逐渐减少，而 Smad3 在 CRC 样本中过表达。综上所述，我们的研究结果表明，miR-140 可能通过靶向 Smad3 抑制 EMT 过程而成为 CRC 进展和转移的关键抑制因子。miR-140 可能是 CRC 治疗的新候选者。