Abstract

BackgroundIncreasing 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.ResultsOur 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.ConclusionTUG1 knockdown overcame DDP resistance of ESCC by epigenetically silencing PDCD4, providing a novel therapeutic target for ESCC.

Highlights

  • Increasing evidence has suggested the involvement of long non-coding RNA taurine upregulated gene 1 (TUG1) in chemoresistance of cancer treatment

  • The results showed that expression of TUG1 was dramatically improved in ECA109 and EC9706 cells compared with HET-1A cells (Fig. 1d, e)

  • The results showed that TUG1 expression was positively associated with enhancer of zeste homolog 2 (EZH2) level in esophageal squamous cell carcinoma (ESCC) tissue samples (Fig. 3a). qRTPCR analysis revealed that TUG1 was mainly located in nucleus of ECA109/DDP cells (Fig. 3b), suggesting that TUG1 may exert its regulatory role at the transcriptional level

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Summary

Introduction

Increasing evidence has suggested the involvement of long non-coding RNA taurine upregulated gene 1 (TUG1) in chemoresistance of cancer treatment. Its function and molecular mechanisms in esophageal squamous cell carcinoma (ESCC) chemoresistance are still not well elucidated. Esophageal squamous cell carcinoma (ESCC) is one of the most frequent gastrointestinal malignancies in human, a sixth most common cause of cancer-related death worldwide [1, 2]. Despite the development of surgery combined with neoadjuvant radiation and/or chemotherapy, the majority of patients with ESCC were diagnosed frequently at the advanced stage and had poor prognosis [3, 4]. Emerging evidence suggests the involvement of lncRNAs in normal development as well as tumorigenesis [8].

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