Double-negative feedback loop between long non-coding RNA TUG1 and miR-145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells

• Published in: FEBS letters Vol. 589; no. 20; pp. 3175 - 3181
• Main Authors: Tan, Jiemei, Qiu, Kaifeng, Li, Mingyi, Liang, Ying
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 07.10.2015
• Subjects: 3' Untranslated Regions - genetics; Aged; Aged, 80 and over; Base Sequence; Bladder cancer; Blotting, Western; Cell Line; Cell Line, Tumor; Epithelial-Mesenchymal Transition - genetics; Epithelial-to-mesenchymal transition; epithelium; Feedback, Physiological; Female; Gene Expression Regulation, Neoplastic; HEK293 Cells; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; Male; metastasis; MicroRNAs - genetics; Middle Aged; miR-145; neoplasm cells; non-coding RNA; radiation resistance; Radiation Tolerance - genetics; Radioresistance; Repressor Proteins - genetics; Repressor Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Sequence Homology, Nucleic Acid; therapeutics; Transplantation, Heterologous; TUG1; urinary bladder neoplasms; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; ZEB2; Zinc Finger E-box Binding Homeobox 2; Radioresistance; ZEB2; TUG1; Bladder cancer; Epithelial-to-mesenchymal transition; miR-145
• DOI: 10.1016/j.febslet.2015.08.020
• ISSN: 0014-5793; 1873-3468

•TUG1 promoted bladder cancer cell invasion and radioresistance through inducing epithelial-to-mesenchymal transition (EMT).•TUG1 decreased the expression of miR-145 and there was a reciprocal repression between TUG1 and miR-145 in an Argonaute2-dependent manner.•TUG1 exerted its function through the miR-145/ZEB2 axis. LncRNAs have a critical role in the regulation of cellular processes such as cancer progression and metastasis. In the present study, we confirmed that TUG1 was overexpressed in bladder cancer tissues and established cell lines. Knockdown of TUG1 inhibited bladder cancer cell metastasis both in vitro and in vivo. Furthermore, we found that TUG1 promoted cancer cell invasion and radioresistance through inducing epithelial-to-mesenchymal transition (EMT). Interestingly, TUG1 decreased the expression of miR-145 and there was a reciprocal repression between TUG1 and miR-145 in an Argonaute2-dependent manner. ZEB2 was identified as a down-stream target of miR-145 and TUG1 exerted its function through the miR-145/ZEB2 axis. In summary, our data indicated that blocking TUG1 function may be an effective anti-cancer therapy.