MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor
In: Gut, Jg. 61 (2011-08-03), S. 33-42
Online
unknown
Zugriff:
To understand the involvement of micro-RNA (miRNA) in the development and progression of oesophageal squamous cell carcinoma (ESCC), miRNA profiles were compared between tumour and corresponding non-tumour tissues.miRCURY LNA array was used to generate miRNA expressing profile. Real-time quantitative PCR was applied to detectthe expression of miR-375 in ESCC samples and its correlation with insulin-like growth factor 1 receptor (IGF1R). Methylation-specific PCR was used to study the methylation status in the promoter region of miR-375. The tumour-suppressive effect of miR-375 was determined by both in-vitro and in-vivo assays.The downregulation of miR-375 was frequently detected in primary ESCC, which was significantly correlated with advanced stage (p=0.003), distant metastasis (p0.0001), poor overall survival (p=0.048) and disease-free survival (p=0.0006). Promoter methylation of miR-375 was detected in 26 of 45 (57.8%) ESCC specimens. Functional assays demonstrated that miR-375 could inhibit clonogenicity, cell motility, cell proliferation, tumour formation and metastasis in mice. Further study showed that miR-375 could interact with the 3'-untranslated region of IGF1R and downregulate its expression. In clinical specimens, the expression of IGF1R was also negatively correlated with miR-375 expression (p=0.008).This study demonstrates that miR-375 has a strong tumour-suppressive effect through inhibiting the expression of IGF1R. The downregulation of miR-375, which is mainly caused by promoter methylation, is one of the molecular mechanisms involved in the development and progression of ESCC.
Titel: |
MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor
|
---|---|
Autor/in / Beteiligte Person: | Xin Yuan Guan ; Chen, Leilei ; Li, Yan ; Kar Lok Kong ; Dora L.W. Kwong ; Law, Simon ; Tim Hon Man Chan ; Yan Ru Qin |
Link: | |
Zeitschrift: | Gut, Jg. 61 (2011-08-03), S. 33-42 |
Veröffentlichung: | BMJ, 2011 |
Medientyp: | unknown |
ISSN: | 1468-3288 (print) ; 0017-5749 (print) |
DOI: | 10.1136/gutjnl-2011-300178 |
Schlagwort: |
|
Sonstiges: |
|