MicroRNA-490-3p inhibits colorectal cancer metastasis by targeting TGFβR1
| Autor: | Xuehu Xu, Shuling Li, Xiaobing Wu, Nanqi Huang, Zhifa Li, Rong Chen, Yong Li, Shangbiao Wu |
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| Rok vydání: | 2015 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty MMP2 Colorectal cancer Receptor Transforming Growth Factor-beta Type I Protein Serine-Threonine Kinases Biology TGF-β signaling Metastasis Cell Movement Cell Line Tumor Internal medicine microRNA Genetics medicine Humans Neoplasm Invasiveness Neoplasm Metastasis Cell Proliferation Gene knockdown Cell growth Cell migration HCT116 Cells Prognosis medicine.disease Survival Analysis digestive system diseases Gene Expression Regulation Neoplastic MicroRNAs Matrix Metalloproteinase 9 Cancer research Matrix Metalloproteinase 2 Signal transduction Colorectal Neoplasms HT29 Cells Receptors Transforming Growth Factor beta Research Article miR-490-3p Signal Transduction |
| Zdroj: | BMC Cancer |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/s12885-015-2032-0 |
| Popis: | Background Colorectal cancer (CRC) is one of the most common malignances worldwide. Metastasis is responsible for the rapid recurrence and poor prognosis of CRC. However, the underlying molecular mechanism of CRC metastasis remains largely unclear. In this study we purposed to investigate the expression and biological functions of miR-490-3p in CRC metastasis, as well as to identify its downstream target genes and influenced pathway. Methods The expression level of miR-490-3p in CRC cell lines, CRC adjacent normal tissues, non-metastasis and metastasis tissues were assessed by quantitative real-time PCR. Patient survivals were follow-up up to 7 years. Gain-of-function and loss-of-function study on cell migration and invasion abilities were carried out by transfection of miR-490-3p mimics or inhibitors respectively. The molecular targets of miR-490-3p were computationally identified and experimentally verified by dual-luciferase reporter assay and western blot. Functional rescue was also conducted to confirm miR-490-3p inhibits CRC metastasis by targeting TGF-β signaling pathway. Results miR-490-3p expression was persistently downregulated during CRC malignant progression, as well as in CRC cell lines. Artificially overexpression miR-490-3p in CRC cell lines inhibited cell migration and invasion abilities while knockdown miR-490-3p expression caused the reverse effects. TGFβR1 and MMP2/9 were the downstream targets of miR-490-3p in CRC. Inhibition of TGFβR1 could partially recover the tumor suppression effect of miR-490-3p. Conclusion miR-490-3p is downregulated during CRC malignant progression. miR-490-3p represses CRC cell migration and invasion abilities, partially by targeting to the TGF-β signaling pathway. Taken together, miR-490-3p is acting as a tumor suppressor in CRC. |
| Databáze: | OpenAIRE |
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