MicroRNA-301b promotes cell invasiveness through targeting TP63 in pancreatic carcinoma cells

被引:57
作者
Funamizu, Naotake [1 ]
Lacy, Curtis Ray [2 ]
Parpart, Sonya T. [3 ]
Takai, Atsushi [4 ]
Hiyoshi, Yukiharu [5 ]
Yanaga, Katsuhiko [1 ]
机构
[1] Jikei Univ, Sch Med, Dept Surg, Tokyo 1058461, Japan
[2] Howard Univ, Sch Med, Washington, DC 20059 USA
[3] Georgetown Univ, Washington, DC USA
[4] Kyoto Univ, Dept Gastroenterol, Kyoto, Japan
[5] Kumamoto Univ, Dept Surg, Kumamoto, Japan
关键词
pancreatic carcinoma; micro-RNA-301b; TP63; EXPRESSION; CANCER; DELTA-NP63-ALPHA; OVEREXPRESSION; TUMORIGENESIS; RESISTANCE; APOPTOSIS; TAP63; P63; P53;
D O I
10.3892/ijo.2014.2243
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Recent studies have demonstrated that deregulated microRNA (miR) expression is implicated in the development of human cancers. In the aberrant miR expression, miR-301 is upregulated in cancers, such as pancreatic, colorectal and oral carcinoma. Based on this evidence, we investigated the contribution of miR-301 to pancreatic carcinoma and the novel target genes of miR-301 in pancreatic carcinoma. In this study, we analyzed the effects of enforced and inhibited expression of miR-301b expression in the Panc-1 and BxPC-3 cell lines. MiR-301b expression levels were associated with cell invasiveness in both cell lines. Additional experiments indicated that miR-301b influences invasiveness through CDH1. Moreover microRNA target search algorithms and experimental strategies suggested that miR-301b suppressed TP63 expression as a novel target of miR-301b. Remarkably, miR-301b was also found to be associated with NF-kappa B activity in both cell lines. In summary, overexpressed miR-301b may suppress TP63 expression and contributes to promote cell invasiveness and to enhance gemcitabine resistance in pancreatic carcinoma cells. Thus, miR-301b may have potential as a novel therapeutic target for cancer treatment due to its stimulatory effects on cell invasiveness.
引用
收藏
页码:725 / 734
页数:10
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