MiR-645 promotes invasiveness, metastasis and tumor growth in colorectal cancer by targeting EFNA5 - 14/03/20
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Highlights |
• | MiR-645 promotes CRC cell migration and invasion in vitro and in vivo. |
• | MiR-645 stimulates the EMT of CRC cells. |
• | EFNA5 mRNA is a direct target of miR-645. |
• | MiR-645 expression inversely correlates with EFNA5 expression in clinical CRC specimens. |
Abstract |
MicroRNA-645 (miR-645) has been implicated in numerous types of human cancers including colon cancer. However, the effects and mechanisms of action of miR-645 dysregulation on the growth and malignancy of colorectal cancer (CRC) remain unclear. In this study, we demonstrated that miR-645 knockdown significantly diminished CRC cell migration and invasion and repressed epithelial–mesenchymal transition (EMT). Conversely, miR-645 overexpression enhanced CRC cell migration, invasion, and EMT. In vivo assays confirmed that miR-645 knockdown substantially reduced CRC growth and metastasis. Regarding the mechanism, ephrin-A5 (EFNA5) was identified as a direct target gene of miR-645. MiR-645 specifically targeted the 3′-untranslated region of EFNA5 mRNA and hindered its expression. EFNA5 knockdown attenuated the effects of miR-645 knockdown on CRC cell migration and invasion. Additionally, we noted a statistically significant inverse correlation between EFNA5 mRNA and miR-645 levels in tumors from 28 patients with CRC. Hence, miR-645 acts as an oncogenic miRNA that may increase CRC cell migration, invasiveness, and metastasis by targeting EFNA5.
Le texte complet de cet article est disponible en PDF.Keywords : MiR-645, EFNA5, Cell invasion, Metastasis, Colorectal cancer
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Vol 125
Article 109889- mai 2020 Retour au numéro
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