MicroRNA-302c represses epithelial–mesenchymal transition and metastasis by targeting transcription factor AP-4 in colorectal cancer - 11/07/18
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Graphical abstract |
Highlights |
• | miR-302c is obviously down-regulated in CRC tissues. |
• | Low miR-302c expression associates with poor clinical outcome of CRC patients. |
• | miR-302c inhibits EMT and metastasis of CRC cells. |
• | TFAP4 is a direct target of miR-302c in CRC. |
• | TFAP4 mediates the tumor suppressive role of miR-302c in CRC. |
Abstract |
MicroRNAs (miRNAs) contribute to tumorigenesis and progression via acting as tumor suppressors or oncogenes in human cancer. Aberrant expression of miR-302c has been reported in various types of cancer except colorectal cancer (CRC). Thus, our study was aimed to verify the expression of miR-302c and its functional role in CRC. We found a significant reduced expression of miR-302c in CRC tissues compared to tumor-adjacent tissues. Low miR-302c level was remarkably correlated with deeper tumor invasion, lymph node metastasis and advanced TNM stage. Importantly, low miR-302c expression was identified as an independent indicator for poor prognosis of CRC patients. Overexpression of miR-302c repressed migration and invasion capacities of SW620 and SW480 cells in vitro. Mechanistically, miR-302c inversely regulated transcription factor AP4 (TFAP4) abundance in both SW620 and SW480 cells, and it negatively correlated with TFAP4 mRNA expression in CRC samples. Herein, TFAP4, a regulator of epithelial-mesenchymal transition (EMT), was recognized as a direct target gene of miR-302c in CRC. Otherwise, miR-302c overexpression increased E-cadherin expression and reduced the levels of Vimentin and SNAI1, suggesting an inhibitory effect of miR-302c on EMT of CRC cells. Notably, our findings established that the EMT and metastasis of Caco-2 cells were enhanced by miR-302c knockdown, and subsequently reversed by TFAP4 silencing. Collectively, these data indicate that miR-302c represses EMT and CRC metastasis possibly by targeting TFAP4, and it may serve as a potential prognostic factor and therapeutic target for CRC.
Le texte complet de cet article est disponible en PDF.Abbreviations : miRNAs, CRC, TFAP4, EMT, mRNAs, 3'-UTR, ERα, NK, ULBP2U, MICA/B, IL8, RACK1, HCC, HCV, siRNA, qRT-PCR, RCC, bHLH, USP22
Keywords : miR-302c, Transcription factor AP4, Colorectal cancer, Epithelial-mesenchymal transition, tumor metastasis
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Vol 105
P. 670-676 - septembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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