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Published on: March 27, 2020

Down-regulation of TERE1/UBIAD1 activated Ras-MAPK signalling and induced cell proliferation

Yanzhi Xia1, Xiong Wei, Shimin Wu

  • 1College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Peoples Republic of China ; †Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China.

Cell Biology International Reports
|November 3, 2012
PubMed

Insights

Decreased TERE1/UBIAD1 expression activates Ras-MAPK signaling, leading to increased cell proliferation in human cancers. This suggests TERE1/UBIAD1 acts as a tumor suppressor by negatively regulating this pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • TERE1/UBIAD1 is implicated in Schnyder crystalline corneal dystrophy and human cancers.
  • The precise molecular mechanisms of TERE1/UBIAD1 in tumorigenesis remain largely undefined.

Purpose of the Study:

  • To investigate the role of TERE1/UBIAD1 in transitional cell carcinoma (TCC) pathogenesis.
  • To elucidate the molecular pathway through which TERE1/UBIAD1 influences cancer cell proliferation.

Main Methods:

  • Quantitative analysis of TERE1/UBIAD1 and hTERT expression in Chinese TCC samples.
  • In vitro knockdown of TERE1 using chemically modified siRNA in L02 cells.
  • Assessment of Ras-MAPK pathway activation (ERK phosphorylation) and hTERT expression.
  • Pharmacological inhibition of the Ras-MAPK pathway using U0126.

Main Results:

  • Reduced TERE1/UBIAD1 expression correlated with elevated hTERT and activated Ras-MAPK signaling in TCC.
  • TERE1 knockdown in L02 cells induced significant cell proliferation, increased hTERT expression, and ERK phosphorylation.
  • MEK inhibition with U0126 reversed these effects, suppressing ERK phosphorylation and hTERT expression.

Conclusions:

  • TERE1/UBIAD1 downregulation activates the Ras-MAPK pathway, promoting cancer cell proliferation.
  • TERE1/UBIAD1 functions as a novel negative regulator of Ras-MAPK signaling.
  • TERE1/UBIAD1 represents a potential therapeutic target for cancers driven by Ras-MAPK pathway dysregulation.
Keywords:
GAPDH, human glyceraldehyde 3-phosphate dehydrogenaseIHC, immunohistochemistryMAPKMAPK, mitogen-activated protein kinaseMC, mock controlMTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromideNC, negative groupSCCD, Schnyder crystalline corneal dystrophySREBP, sterol response element binding proteinTCC, transitional cell carcinomaTERE1/UBIAD1cell proliferationhTERTsiRNA, small interfering RNA

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