In:
Cancer Science, Wiley, Vol. 104, No. 12 ( 2013-12), p. 1609-1617
Abstract:
Micro RNA s (mi RNA s), which negatively regulate protein expression by binding protein‐coding mRNA s, have been integrated into cancer development and progression as either oncogenes or tumor suppressor genes. mi R ‐30c was reported to be downregulated in several types of cancer. However, its role in human renal cell carcinoma ( RCC ) remains largely unknown. Here, we show that mi R ‐30c is significantly downregulated in human RCC tissues and cell lines. We found that miR‐30c downregulation could be induced by hypoxia in RCC cells in a hypoxia‐inducible factors ( HIF s) dependent manner. Repression of mi R ‐30c through its inhibitor resulted in reduction of E ‐cadherin production and promotion of epithelial‐mesenchymal transition ( EMT ), while overexpression of mi R ‐30c inhibited EMT in RCC cells. We identified Slug as a direct target of mi R ‐30c in RCC cells. Slug was upregulated in RCC tissues and its expression could be induced by hypoxia, which is consistent with downregulation of mi R ‐30c by hypoxia. Forced overexpression of S lug in 786‐ O cells reduced E ‐cadherin production, and promoted EMT as well as cell migration. Moreover, Slug overexpression abrogated the inhibitory role of mi R ‐30c in regulating EMT and cell migration, indicating mi R ‐30c regulates EMT through Slug in RCC cells. Our findings propose a model that hypoxia induces EMT in RCC cells through downregulation of mi R ‐30c, which leads to subsequent increase of S lug expression and repression of E ‐cadherin production, and suggest a potential application of mi R ‐30c in RCC treatment.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2013.104.issue-12
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
