肾细胞肾癌中mi-RNA218表达通路
作者：Takeshi Yamasaki, Naohiko Seki, Hirofumi Yoshino, Toshihiko Itesako, et al. 来源：Journal of Urology 日期：2013-03-12
导读
microRNA-218 inhibits cell migration and invasion in renal cell carcinoma through targeting caveolin-2 involved in focal adhesion pathway
Abstract
Purpose:
Our microRNA (miRNA) expression signature of renal cell carcinoma (RCC) revealed that miR-218expression was significantly reduced in cancer tissues, suggesting miR-218was a candidate tumor suppressor. The aim of this study was to investigate the functional significance of miR-218in cancer cells and to identify novel miR-218-mediated cancer pathways in RCC.
Materials and Methods:
Gain-of-function studies using mature miR-218were performed to investigate cell proliferation, migration and invasion in RCC cell lines (A498 and 786-O). To identify miR-218-mediated molecular pathways and responsible genes in RCC, we adopted gene expression analyses and in silico database analyses. Loss-of-function assays were performed to investigate the functional significance of miR-218target genes.
Results:
Restoration of mature miR-218significantly inhibited cell proliferation, migration and invasion in RCC cells. Gene expression studies and luciferase reporter assays showed that caveolin-2 ( CAV2) involved in focal adhesion pathway was directly regulated by miR-218. Silencing study of CAV2demonstrated significant inhibition of cell proliferation, migration and invasion. The mRNA and protein expression of CAV2 were significantly upregulated in RCC clinical specimens.
Conclusions:
Loss of tumor suppressive miR-218 enhances cancer cell migration and invasion through dysregulation of the focal adhesion pathway, especially CAV2 as an oncogenic function in RCC. Tumor suppressive miRNA-mediated cancer pathways and responsible genes provide new insights into the potential mechanisms of RCC oncogenesis and metastasis.
http://www.jurology.com/article/S0022-5347(13)00365-0/abstract
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