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

Abstract

a b s t r a c tLncRNAs 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.

Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment

“…3a–d). Intriguingly, the interaction between TUG1 and miR-145, which induced epithelial-to-mesenchymal transition through derepression of ZEB2, has been found in bladder cancer16. Consistently, RNA-FISH analysis revealed that numbers of TUG1 molecules were extremely abundant compared with those of miR-145 molecules in GSCs, whereas they were significantly increased by TUG1 inhibition (Fig.…”

“…Notably, as determined by RNA immunoprecipitation (RIP) analysis, both TUG1 and miR-145 bound to wild-type AGO2 but did not bind to a mutant form of AGO2 devoid of the PAZ domain, the latter serving as a module for si/miRNA transfer in the RNA silencing pathway and as an anchoring site for the 3′ end of guide RNA within silencing effector complexes (Supplementary Fig. 5c,d)1628.…”

“…TUG1 was originally identified as a transcript upregulated by taurine, whose function is associated with retinal development15. In the context of human malignancies, it is overexpressed in bladder cancer, gastric cancer and osteosarcoma161718, whereas it is downregulated in non-small cell lung cancer19, suggesting context-dependent roles in different types of cancers. As the length of the TUG1 lncRNA is not short, ∼7.1 kb, it is plausible that TUG1 has multiple functions, which remain unknown.…”

Long noncoding RNA Tug1 regulates mitochondrial bioenergetics in diabetic nephropathy

“…Consistent with previously published data, our findings suggest that Tug1 localizes to both the cytoplasm and the nucleus. While we have focused on the role of Tug1 in the nucleus in this study, it has been previously shown that cytoplasmic Tug1 could act as a competitive endogenous RNA (ceRNA) for certain miRs (60,61), as well as play a role in the translational stability of mRNAs (62). Further studies are needed to unravel the cytoplasmic function of Tug1 in podocytes and the interplay between cytoplasmic versus nuclear Tug1 in regulating mitochondrial bioenergetics.…”

High TUG1 expression is associated with chemotherapy resistance and poor prognosis in esophageal squamous cell carcinoma

“…Upregulation of TUG1 may confer anticancer drug resistance to cancer cells by overactivation of the PIK3/AKT signaling pathway. Furthermore, TUG1 promotes cancer cell invasion, metastasis, and radioresistance by through inducing epithelial-to-mesenchymal transition [10,31]. These may partly explain why patients with high TUG1 expression have poor prognosis.…”