To determine the inhibitory effect of miRNA-381 on renal carcinoma invasion and to explore the underlying mechanisms.
After up-regulation of miRNA-381, the inhibitory effect of miR-381 on cell invasion was investigated.
We screened the target genes of miRNA-381 in a database (starBase) through combination of five programs including targetscan, picTar, RNA22, PITA and miRanda. Then, the predicted targeting genes were verified by the dual luciferase reporter assay. We also examined the expression of miRNA-381 and its target genes in renal cancer cells and tissues.
Transfection and up-regulation of miRNA-381 resulted in a significant decrease in trans-membrane cell numbers and the ability of renal cell invasion. Bioinformatics analysis showed that CREB binding protein (CBP), β-catenin and lymphoid enhancer binding factor-1 (LEF-1) were the potential targets of miRNA-381. In the luciferase reporter gene system, co-transfection of miRNA-381 with the 3'UTR of wild-type target gene led to a significant decrease in luciferase activity. The expression of miRNA-381 was decreased in various renal cancer cells, and it was particularly lower in highly metastatic cell lines (786-OHM). On the contrary, the expression levels of miRNA-381 target genes (CBP, β-catenin and LEF-1) were significantly increased in cells and tissues.
MiRNA-381 can inhibit cell invasion in renal cancer by block the function of CBP, β-catenin and LEF-1.
Abstract available from the publisher.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences. 2015 Oct 28 [Epub]
Binghai Chen, Bin Liu
Department of Urology, Affiliated Hospital of Jiangsu University, Zhenjiang Jiangsu 212000, China. , Department of Urology, Third Xiangya Hospital, Changsha 410013, China.