OncoTargets and Therapy (Jul 2019)

LSD1 regulates Notch and PI3K/Akt/mTOR pathways through binding the promoter regions of Notch target genes in esophageal squamous cell carcinoma

  • Hou G,
  • Zhao Q,
  • Zhang M,
  • Wang P,
  • Ye H,
  • Wang Y,
  • Ren Y,
  • Zhang J,
  • Lu Z

Journal volume & issue
Vol. Volume 12
pp. 5215 – 5225

Abstract

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Guiqin Hou,1 Qi Zhao,1 Mengying Zhang,1 Peng Wang,2 Hua Ye,2 Yang Wang,1 Yandan Ren,1 Jianying Zhang2,3 Zhaoming Lu11School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 2College of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 3Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of ChinaBackground: The aberrant activation of Lysine-specific demethylase 1(LSD1), Notch and PI3K/Akt/mTOR signaling pathways were frequently happened in many cancers, including esophageal squamous cell carcinoma (ESCC). However, the regulatory relationship between LSD1 and Notch as well as PI3K/Akt/mTOR pathways is still unclear.Purpose: This study aimed to explore the regulatory effects and mechanisms of LSD1 on Notch and PI3K/Akt/mTOR pathway in ESCC.Results: Firstly, we demonstrated that LSD1 and proteins in Notch and PI3K/Akt/mTOR pathway were expressed in ESCC cells. Secondly, inhibition of LSD1 by tranylcypromine (TCP) or shRNA could decrease the expressions of related proteins in Notch and PI3K/Akt/mTOR signaling pathways in ESCC cells. Finally, we found that LSD1 could bind to the promoter regions of Notch3, Hes1 and CR2, and the combinations between them were reduced by TCP in ESCC.Conclusion: Summarily, this study indicated that LSD1 might positively regulate Notch and PI3K/Akt/mTOR pathways through binding the promoter regions of related genes in Notch pathway in ESCC.Keywords: LSD1, Notch, PI3K/Akt/mTOR, esophageal squamous cell carcinoma

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