title: Overexpression of long non-coding RNA TUG1 predicts poor prognosis and promotes cancer cell proliferation and migration in high-grade muscle-invasive bladder cancer.
abstract: Long non-coding RNA TUG1 is involved in the development and progression of a variety of tumors. Little is known about TUG1 function in high-grade muscle-invasive bladder cancer (MIBC). The aims of our study were to determine expression levels of long non-coding RNA TUG1 in tumor tissue, to evaluate its relationship with clinico-pathological features of high-grade MIBC, and to describe its function in MIBC cells in vitro. TUG1 expression levels were determined in paired tumor and adjacent non-tumor bladder tissues of 47 patients with high-grade MIBC using real-time PCR. Cell line T-24 and siRNA silencing were used to study the TUG1 function in vitro. We observed significantly increased levels of TUG1 in tumor tissue in comparison to adjacent non-tumor bladder tissue (P < 0.0001). TUG1 levels were significantly increased in metastatic tumors (P = 0.0147) and were associated with shorter overall survival of MIBC patients (P = 0.0241). TUG1 silencing in vitro led to 34 % decrease in cancer cell proliferation (P = 0.0004) and 23 % reduction in migration capacity of cancer cells (P < 0.0001). We did not observe any significant effects of TUG1 silencing on cell cycle distribution and number of apoptotic cells. Our study confirmed overexpression of TUG1 in MIBC tumor tissue and described its association with worse overall survival in high-grade MIBC patients. Together with in vitro observations, these data suggest an oncogenic role of TUG1 and its potential usage as biomarker or therapeutic target in MIBC.
authors.affiliation: Central European Institute of Technology (CEITEC), Masaryk University, University Campus Bohunice, Building A35, Room 217, Kamenice 5, 625 00, Brno, Czech Republic.
authors.forename: Robert
authors.initials: R
authors.lastname: Iliev
authors.affiliation: Central European Institute of Technology (CEITEC), Masaryk University, University Campus Bohunice, Building A35, Room 217, Kamenice 5, 625 00, Brno, Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Kleinova
authors.affiliation: 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, Zluty kopec 7, Brno, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Juracek
authors.affiliation: Department of Urologic Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53, Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Dolezel
authors.affiliation: Central European Institute of Technology (CEITEC), Masaryk University, University Campus Bohunice, Building A35, Room 217, Kamenice 5, 625 00, Brno, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Ozanova
authors.affiliation: Department of Urology, University Hospital Brno and Masaryk University Brno, Jihlavska 20, 62500, Brno, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Fedorko
authors.affiliation: Department of Urology, University Hospital Brno and Masaryk University Brno, Jihlavska 20, 62500, Brno, Czech Republic.
authors.forename: Dalibor
authors.initials: D
authors.lastname: Pacik
authors.affiliation: 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, Zluty kopec 7, Brno, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Svoboda
authors.affiliation: Department of Urologic Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53, Brno, Czech Republic. stanik@mou.cz.
authors.forename: Michal
authors.initials: M
authors.lastname: Stanik
authors.affiliation: 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, Zluty kopec 7, Brno, Czech Republic. on.slaby@gmail.com.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Slaby
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics*; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019042:Muscle Neoplasms / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C000598536:TUG1 long noncoding RNA, human
keywords: Long non-coding RNA; Migration; Muscle-invasive bladder cancer; Prognosis; Proliferation; TUG1