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
相关论文
共 33 条
[1]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[2]   Intronic miR-301 feedback regulates its host gene, ska2, in A549 cells by targeting MEOX2 to affect ERK/CREB pathways [J].
Cao, Guojun ;
Huang, Baochun ;
Liu, Zhaohui ;
Zhang, Jiyan ;
Xu, Hua ;
Xia, Wei ;
Li, Jie ;
Li, Shaohua ;
Chen, Liucun ;
Ding, Hongmei ;
Zhao, Qiang ;
Fan, Ming ;
Shen, Beifen ;
Shao, Ningsheng .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2010, 396 (04) :978-982
[3]   Overexpression of ΔNp63 in a Human Nasopharyngeal Carcinoma Cell Line Downregulates CKIs and Enhances Cell Proliferation [J].
Chiang, Chi-Tai ;
Chu, Wing-Keung ;
Chow, Shu-Er ;
Chen, Jan-Kan .
JOURNAL OF CELLULAR PHYSIOLOGY, 2009, 219 (01) :117-122
[4]   NF-κB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells:: potential involvement of ZEB-1 and ZEB-2 [J].
Chua, H. L. ;
Bhat-Nakshatri, P. ;
Clare, S. E. ;
Morimiya, A. ;
Badve, S. ;
Nakshatri, H. .
ONCOGENE, 2007, 26 (05) :711-724
[5]   Meta-analysis of Phase III randomized trials of molecular targeted therapies for advanced pancreatic cancer [J].
Eltawil, Karim M. ;
Renfrew, Paul D. ;
Molinari, Michele .
HPB, 2012, 14 (04) :260-268
[6]   Tetrahydrouridine Inhibits Cell Proliferation through Cell Cycle Regulation Regardless of Cytidine Deaminase Expression Levels [J].
Funamizu, Naotake ;
Lacy, Curtis Ray ;
Fujita, Kaori ;
Furukawa, Kenei ;
Misawa, Takeyuki ;
Yanaga, Katsuhiko ;
Manome, Yoshinobu .
PLOS ONE, 2012, 7 (05)
[7]   Hydroxyurea Decreases Gemcitabine Resistance in Pancreatic Carcinoma Cells With Highly Expressed Ribonucleotide Reductase [J].
Funamizu, Naotake ;
Kamata, Yuko ;
Misawa, Takeyuki ;
Uwagawa, Tadashi ;
Lacy, Curtis Ray ;
Yanaga, Katsuhiko ;
Manome, Yoshinobu .
PANCREAS, 2012, 41 (01) :107-113
[8]   Is the resistance of gemcitabine for pancreatic cancer settled only by overexpression of deoxycytidine kinase? [J].
Funamizu, Naotake ;
Okamoto, Aikou ;
Kamata, Yuko ;
Misawa, Takeyuki ;
Uwagawa, Tadashi ;
Gocho, Takeshi ;
Yanaga, Katsuhiko ;
Manome, Yoshinobu .
ONCOLOGY REPORTS, 2010, 23 (02) :471-475
[9]   RETRACTED: EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers (Retracted Article) [J].
Garofalo, Michela ;
Romano, Giulia ;
Di Leva, Gianpiero ;
Nuovo, Gerard ;
Jeon, Young-Jun ;
Ngankeu, Apollinaire ;
Sun, Jin ;
Lovat, Francesca ;
Alder, Hansjuerg ;
Condorelli, Gerolama ;
Engelman, Jeffrey A. ;
Ono, Mayumi ;
Rho, Jin Kyung ;
Cascione, Luciano ;
Volinia, Stefano ;
Nephew, Kenneth P. ;
Croce, Carlo M. .
NATURE MEDICINE, 2012, 18 (01) :74-82
[10]   TAp63α induces apoptosis by activating signaling via death receptors and mitochondria [J].
Gressner, O ;
Schilling, T ;
Lorenz, K ;
Schleithoff, ES ;
Koch, A ;
Schulze-Bergkamen, H ;
Lena, AM ;
Candi, E ;
Terrinoni, A ;
Catani, MV ;
Oren, M ;
Melino, G ;
Krammer, PH ;
Stremmel, W ;
Müller, M .
EMBO JOURNAL, 2005, 24 (13) :2458-2471