A significant role of transcription factors E2F in inflammation and tumorigenesis of nasopharyngeal carcinoma

Biochem Biophys Res Commun. 2020 Apr 16;524(4):816-824. doi: 10.1016/j.bbrc.2020.01.158. Epub 2020 Feb 7.

Abstract

Nasopharyngeal carcinoma (NPC) is a malignant tumor from head and neck with characteristics in remarkable geographic and racial distribution worldwide, which has the important features of vigorous proliferation and inflammatory cells infiltration. By analyzing the expression profile data of NPC, we found that the E2F-related gene sets were highly enriched in NPC tissues. E2F transcription factor family is an important cycle regulator, which can promote the malignant proliferation and tumorigenesis. Here, we showed that E2Fs accelerated malignant phenotypes of NPC cells. RNA sequencing revealed that E2Fs can significantly up-regulate the inflammatory pathways in NPC cells. E2F1, as a transcription factor, can active the transcription activity of IL-6 promoter, and modulate macrophage function through a microenvironment manner. Thus, this study characterized a significant role of E2Fs in inflammation and tumorigenesis of NPC, which provided a promising anti-tumor target in NPC, since E2Fs are highly expressed and activated in NPC.

Keywords: E2F1; E2F3; Inflammation; Interleukin 6; Nasopharyngeal carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cohort Studies
  • E2F1 Transcription Factor / antagonists & inhibitors
  • E2F1 Transcription Factor / genetics*
  • E2F1 Transcription Factor / metabolism
  • E2F3 Transcription Factor / antagonists & inhibitors
  • E2F3 Transcription Factor / genetics*
  • E2F3 Transcription Factor / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Inflammation
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Nude
  • Nasopharyngeal Carcinoma / genetics*
  • Nasopharyngeal Carcinoma / metabolism
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • THP-1 Cells
  • Tumor Burden
  • Tumor Microenvironment / genetics

Substances

  • E2F1 Transcription Factor
  • E2F1 protein, human
  • E2F3 Transcription Factor
  • E2F3 protein, human
  • IL6 protein, human
  • Interleukin-6
  • RNA, Small Interfering