MiR-429 is linked to metastasis and poor prognosis in renal cell carcinoma by affecting epithelial-mesenchymal transition.
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-β 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-β-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.
Central European Institute of Technology (CEITEC), Masaryk University, University Campus Bohunice, Building A35, Room 217, Kamenice 5, 625 00, Brno, Czech Republic.
Tana
T
Machackova
Central European Institute of Technology (CEITEC), Masaryk University, University Campus Bohunice, Building A35, Room 217, Kamenice 5, 625 00, Brno, Czech Republic.
Hana
H
Mlcochova
Department of Urologic Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Michal
M
Stanik
Department of Urologic Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Jan
J
Dolezel
Department of Urology, University Hospital Brno and Masaryk University, Brno, Czech Republic.
Michal
M
Fedorko
Department of Urology, University Hospital Brno and Masaryk University, Brno, Czech Republic.
Dalibor
D
Pacik
Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Alexandr
A
Poprach
Central European Institute of Technology (CEITEC), Masaryk University, University Campus Bohunice, Building A35, Room 217, Kamenice 5, 625 00, Brno, Czech Republic.|Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Marek
M
Svoboda
Central European Institute of Technology (CEITEC), Masaryk University, University Campus Bohunice, Building A35, Room 217, Kamenice 5, 625 00, Brno, Czech Republic. on.slaby@gmail.com.|Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic. on.slaby@gmail.com.
Ondrej
O
Slaby
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015820:Cadherins / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000556:secondary* / Q000628:therapy; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000235:genetics; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; C546363:MIRN429 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta
E-cadherin; Epithelial-mesenchymal transition; Renal cell carcinoma; miR-429; microRNA