MicroRNA-140 Inhibits the Epithelial-Mesenchymal Transition and Metastasis in Colorectal Cancer

作者：Li, Jiazhi; Zou, Kun; Yu, Lihui; Zhao, Wenyue; Lu, Ying; Mao, Jun; Wang, Bo; Wang, Lu; Fan, Shujun; Song, Bo^*; Li, Lianhong^*

来源：Molecular Therapy - Nucleic Acids, 2018, 10: 426-437.

DOI：10.1016/j.omtn.2017.12.022

• TGF-BETA
• STEM-CELL
• SMAD3
• EXPRESSION
• PROTEINS
• INVASION
• GROWTH
• PATHOGENESIS
• PROGRESSION
• MIR-140

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-beta 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.

• 出版日期2018-3-10
• 单位大连医科大学