TUG1 confers cisplatin resistance in esophageal squamous cell carcinoma by epigenetically suppressing PDCD4 expression via EZH2

TUG1 通过 EZH2 表观遗传抑制 PDCD4 表达,导致食管鳞状细胞癌产生顺铂耐药性

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作者:Caihui Xu, Yinmou Guo, Haiyan Liu, Gongbin Chen, Yanju Yan, Teng Liu

Background

Increasing evidence has suggested the involvement of long non-coding RNA taurine upregulated gene 1 (TUG1) in chemoresistance of cancer treatment. However, its function and molecular mechanisms in esophageal squamous cell carcinoma (ESCC) chemoresistance are still not well elucidated. In the present study, we investigate the functional role of TUG1 in cisplatin (DDP) resistance of ESCC and discover the underlying molecular mechanism.

Conclusion

TUG1 knockdown overcame DDP resistance of ESCC by epigenetically silencing PDCD4, providing a novel therapeutic target for ESCC.

Results

Our study revealed that TUG1 was up-regulated in DDP-resistant ESCC tissues and cells. High TUG1 expression was correlated with poor prognosis of ESCC patients. TUG1 knockdown improved the sensitivity of ECA109/DDP and EC9706/DDP cells to DDP. Moreover, TUG1 could epigenetically suppress PDCD4 expression via recruiting enhancer of zeste homolog 2. PDCD4 overexpression could mimic the functional role of down-regulated TUG1 in DDP resistance. PDCD4 knockdown counteracted the inductive effect of TUG1 inhibition on DDP sensitivity of ECA109/DDP and EC9706/DDP cells. Furthermore, TUG1 knockdown facilitated DDP sensitivity of DDP-resistant ESCC cells in vivo.

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