MiR-429 is linked to metastasis and poor prognosis in renal cell carcinoma by affecting epithelial-mesenchymal transition

被引：41
作者：
Machackova, Tana [1 ]
Mlcochova, Hana [1 ]
Stanik, Michal [2 ]
Dolezel, Jan [2 ]
Fedorko, Michal [3 ,4 ]
Pacik, Dalibor [3 ,4 ]
Poprach, Alexandr [5 ]
Svoboda, Marek [1 ,5 ]
Slaby, Ondrej [1 ,5 ]
机构：
[1] Masaryk Univ, Cent European Inst Technol CEITEC, Univ Campus Bohunice,Bldg A35,Room 217,Kamenice 5, Brno 62500, Czech Republic
[2] Masaryk Mem Canc Inst, Dept Urol Oncol, Brno, Czech Republic
[3] Univ Hosp Brno, Dept Urol, Brno, Czech Republic
[4] Masaryk Univ, Brno, Czech Republic
[5] Masaryk Mem Canc Inst, Dept Comprehens Canc Care, Brno, Czech Republic
来源：
TUMOR BIOLOGY | 2016年 / 37卷 / 11期
关键词：
Renal cell carcinoma; Epithelial-mesenchymal transition; microRNA; miR-429; E-cadherin; GASTRIC-CANCER CELLS; DOWN-REGULATION; INVASION; ZEB1; INHIBITION; EXPRESSION; MIGRATION; GROWTH;
D O I：
10.1007/s13277-016-5310-9
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
MicroRNAs (miRNAs) have been proven to be important oncogenes and tumor suppressors in wide range of cancers, including renal cell carcinoma (RCC). In our study, we evaluated miRNA-429 as potential diagnostic/prognostic biomarker in 172 clear cell RCC patients and as a potential regulator of epithelial-mesenchymal transition (EMT) in vitro. We demonstrated that miR-429 is down-regulated in tumor tissue samples (P < 0.0001) and is significantly associated with cancer metastasis (P < 0.0001), shorter disease-free (P = 0.0105), and overall survival (P = 0.0020). In addition, ectopic expression of miR-429 in 786-0 RCC cells followed by TGF-beta treatment led to increase in the levels of E-cadherin expression (P < 0.0001) and suppression of cellular migration (P < 0.0001) in comparison to TGF-beta-treated controls. Taken together, our findings suggest that miR-429 may serve as promising diagnostic and prognostic biomarker in RCC patients. We further suggest that miR-429 has a capacity to inhibit loss of E-cadherin in RCC cells undergoing EMT and consequently attenuate their motility.
引用
收藏
页码：14653 / 14658
页数：6
相关论文
共 30 条
[1]   A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition [J].
Bracken, Cameron P. ;
Gregory, Philip A. ;
Kolesnikoff, Natasha ;
Bert, Andrew G. ;
Wang, Jun ;
Shannon, M. Frances ;
Goodall, Gregory J. .
CANCER RESEARCH, 2008, 68 (19) :7846-7854
[2]   Renal cell carcinoma [J].
Cairns, Paul .
CANCER BIOMARKERS, 2011, 9 (1-6) :461-473
[3]   Loss of miR-200c Expression Induces an Aggressive, Invasive, and Chemoresistant Phenotype in Non-Small Cell Lung Cancer [J].
Ceppi, Paolo ;
Mudduluru, Giridhar ;
Kumarswamy, Regalla ;
Rapa, Ida ;
Scagliotti, Giorgio V. ;
Papotti, Mauro ;
Allgayer, Heike .
MOLECULAR CANCER RESEARCH, 2010, 8 (09) :1207-1216
[4]   Regulation of cancer metastasis by microRNAs [J].
Chan, Shih-Hsuan ;
Wang, Lu-Hai .
JOURNAL OF BIOMEDICAL SCIENCE, 2015, 22
[5]   miR-200b inhibits TGF-β1-induced epithelial-mesenchymal transition and promotes growth of intestinal epithelial cells [J].
Chen, Y. ;
Xiao, Y. ;
Ge, W. ;
Zhou, K. ;
Wen, J. ;
Yan, W. ;
Wang, Y. ;
Wang, B. ;
Qu, C. ;
Wu, J. ;
Xu, L. ;
Cai, W. .
CELL DEATH & DISEASE, 2013, 4 :e541-e541
[6]   TGF-β promotes invasion and metastasis of gastric cancer cells by increasing fascin1 expression via ERK and JNK signal pathways [J].
Fu, Hua ;
Hu, Zhongliang ;
Wen, Jifang ;
Wang, Kuansong ;
Liu, Ying .
ACTA BIOCHIMICA ET BIOPHYSICA SINICA, 2009, 41 (08) :648-656
[7]   A unique set of 6 circulating microRNAs for early detection of non-small cell lung cancer [J].
Halvorsen, Ann Rita ;
Bjaanaes, Maria ;
LeBlanc, Marissa ;
Holm, Are M. ;
Bolstad, Nils ;
Rubio, Luis ;
Penalver, Juan Carlos ;
Cervera, Jose ;
Mojarrieta, Julia Cruz ;
Lopez-Guerrero, Jose Antonio ;
Brustugun, Odd Terje ;
Helland, Aslaug .
ONCOTARGET, 2016, 7 (24) :37250-37259
[8]   MiR-338-3p inhibits epithelial-mesenchymal transition in gastric cancer cells by targeting ZEB2 and MACC1/Met/Akt signaling [J].
Huang, Na ;
Wu, Zhenzhen ;
Lin, Li ;
Zhou, Minyu ;
Wang, Lin ;
Ma, Huanrong ;
Xia, Jianling ;
Bin, Jianping ;
Liao, Yulin ;
Liao, Wangjun .
ONCOTARGET, 2015, 6 (17) :15222-15234
[9]   TGF-β1-induced Fascin1 promotes cell invasion and metastasis of human 786-0 renal carcinoma cells [J].
Huang, Wei ;
Cen, Son ;
Kang, Xin-Li ;
Wang, Wei-Fu ;
Wang, Yang ;
Chen, Xiang .
ACTA HISTOCHEMICA, 2016, 118 (02) :144-151
[10]   miR-629 Targets TRIM33 to Promote TGFβ/Smad Signaling and Metastatic Phenotypes in ccRCC [J].
Jingushi, Kentaro ;
Ueda, Yuko ;
Kitae, Kaori ;
Hase, Hiroaki ;
Egawa, Hiroshi ;
Ohshio, Ikumi ;
Kawakami, Ryoji ;
Kashiwagi, Yuri ;
Tsukada, Yohei ;
Kobayashi, Takumi ;
Nakata, Wataru ;
Fujita, Kazutoshi ;
Uemura, Motohide ;
Nonomura, Norio ;
Tsujikawa, Kazutake .
MOLECULAR CANCER RESEARCH, 2015, 13 (03) :565-574
123