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Development of Compendium for Esophageal Squamous Cell Carcinoma
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Development of Compendium for Esophageal Squamous Cell Carcinoma

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

Caihui Xu1, Yinmou Guo1, Haiyan Liu1

  • 11Department of Oncology, Shangqiu First People's Hospital, No. 292 Kaixuan South Road, Shangqiu, 476100 China.

Cell & Bioscience
|December 7, 2018
PubMed
Abstract

Insights

Knocking down long non-coding RNA TUG1 (taurine upregulated gene 1) resensitizes esophageal squamous cell carcinoma (ESCC) to cisplatin by epigenetically silencing PDCD4. This offers a new therapeutic strategy for ESCC chemoresistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Long non-coding RNA taurine upregulated gene 1 (TUG1) is implicated in cancer chemoresistance.
  • The specific role and mechanisms of TUG1 in esophageal squamous cell carcinoma (ESCC) cisplatin resistance remain unclear.

Purpose of the Study:

  • To investigate the function of TUG1 in cisplatin (DDP) resistance in ESCC.
  • To elucidate the molecular mechanisms underlying TUG1's role in ESCC chemoresistance.

Main Methods:

  • Analysis of TUG1 expression in DDP-resistant ESCC tissues and cells.
  • TUG1 knockdown experiments in ESCC cell lines (ECA109/DDP, EC9706/DDP) and in vivo models.
  • Investigation of the epigenetic regulation of PDCD4 by TUG1 via enhancer of zeste homolog 2 (EZH2).
  • Assessment of PDCD4's role in mediating TUG1's effect on DDP sensitivity.

Main Results:

  • TUG1 expression was elevated in DDP-resistant ESCC tissues and cells, correlating with poor prognosis.
  • TUG1 knockdown enhanced ESCC cell sensitivity to DDP.
  • TUG1 epigenetically suppressed PDCD4 expression by recruiting EZH2.
  • PDCD4 overexpression mimicked TUG1 knockdown effects, while PDCD4 knockdown reversed TUG1 inhibition's impact on DDP sensitivity.
  • TUG1 knockdown improved DDP sensitivity in vivo.

Conclusions:

  • TUG1 knockdown overcomes cisplatin resistance in ESCC by epigenetically silencing PDCD4.
  • TUG1 represents a potential therapeutic target for overcoming DDP resistance in esophageal squamous cell carcinoma.
Keywords:
CisplatinEnhancer of zeste homolog 2Esophageal squamous cell carcinomaPDCD4Taurine upregulated gene 1

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