MicroRNA-302c represses epithelial-mesenchymal transition and metastasis by targeting transcription factor AP-4 in colorectal cancer.

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.

• Authors: Wenqi Ma, Bailing Liu, Jie Li, Jue Jiang, Ru Zhou, Lili Huang, Xiaopeng Li, Xin He, Qi Zhou
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 105 Pg. 670-676 (Sep 2018) ISSN: 1950-6007 [Electronic] France
• PMID: 29906744 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical References

• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• DNA-Binding Proteins
• MIRN302A microRNA, human
• MicroRNAs
• REPIN1 protein, human
• RNA-Binding Proteins

Topics

• Aged
• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors (genetics)
• Caco-2 Cells
• Cell Movement (genetics)
• Colorectal Neoplasms (genetics, pathology)
• DNA-Binding Proteins
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Humans
• Male
• MicroRNAs (genetics)
• Middle Aged
• Neoplasm Invasiveness (genetics)
• Neoplasm Metastasis
• RNA-Binding Proteins