MiR-199a-5p loss up-regulated DDR1 aggravated colorectal cancer by activating epithelial-to-mesenchymal transition related signaling.
Dig Dis Sci
; 59(9): 2163-72, 2014 Sep.
Article
en En
| MEDLINE
| ID: mdl-24711074
ABSTRACT
BACKGROUND:
Discoidin domain receptors1 (DDR1) is associated with tumor progression, and its dysregulated expression has been observed in many cancers.AIM:
We aim to explore molecular mechanism underlying the role of DDR1 in colorectal cancer development.METHODS:
Immunohistochemistry and Western blot were applied to examine the DDR1 expression. Real-time RT-PCR and Western blot were performed to determine the expression of miR-199a-5p and DDR1. Luciferase reporter assay was used to determine whether DDR1 was a target of miR-199a-5p. Effects of miR-199a-5p and DDR1 on colorectal cell proliferation, colony formation, cell cycle progression, invasion and migration were then investigated. Western blot was used to determine the relative signal pathways.RESULTS:
Increased DDR1 and decreased miR-199a-5p expression coexisted in CRC, knockdown of DDR1 or overexpression of miR-199a-5p both resulted in reduced colony formation, invasive and migratory capabilities of human CRC LOVE1 and LOVO cells. It was also found that overexpression of miR-199a-5p led to decreased DDR1, MMP2, N-cadherin and vimentin expression and increased E-cadherin expression in both CRC cell lines. However, down-regulation of miR-199a-5p resulted in the opposite effects. Dual luciferase reporter assay confirmed that miR-199a-5p could directly target DDR1 through binding to its 3'-UTR.CONCLUSIONS:
Our findings indicated that up-regulation of DDR1 induced by miR-199a-5p down-regulation may contribute to the development and progression of CRC, and this effect may be associated with increased invasiveness, at least in part, via activating the EMT-related signaling.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ARN Mensajero
/
Neoplasias Colorrectales
/
Proteínas Tirosina Quinasas Receptoras
/
MicroARNs
/
Transición Epitelial-Mesenquimal
Límite:
Humans
Idioma:
En
Año:
2014
Tipo del documento:
Article