The RNA binding protein tristetraprolin down-regulates autophagy in lung adenocarcinoma cells

Exp Cell Res. 2018 Jun 1;367(1):89-96. doi: 10.1016/j.yexcr.2018.03.028. Epub 2018 Mar 22.

Abstract

Tristetraprolin (TTP) is the most well-known member of RNA-binding zinc-finger protein that play a significant role in accelerating mRNA decay. Increasingly studies have reported that TTP was functioned as a tumor suppressor gene in several types of carcinomas, while its underlying mechanism is not clear yet. In the current study, we found that TTP overexpression decreased cell proliferation and increased cell death in lung adenocarcinoma cells, with the cell cycle arrest at the S phase. Remarkably, instead of inducing cell apoptosis directly, TTP overexpression alters cell autophagy. Our studies demonstrate that TTP overexpression has no effect on apoptosis related genes, but decreases the expression of autophagy-related genes, including Beclin 1 and LC3II. The level of autophagy flux assessed by infection with the mGFP-RFP-LC3 adenovirus construction has been blocked by TTP overexpression. Moreover, the autophagic vacuoles number detected by transmission electron microscopy decreased with TTP expression up-regulation. Our results indicate, for the first time, that TTP suppresses cell proliferation and increases cell death through cell autophagy pathway in lung cancer cells. Our study provides a new angle of view for TTP function as a tumor suppressor which could be targeted in tumor treatment.

Keywords: Autophagy; Cell proliferation; Lung adenocarcinoma; RNA binding protein; Tristetraprolin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / metabolism
  • Adenocarcinoma of Lung / pathology*
  • Apoptosis
  • Autophagy*
  • Cell Cycle
  • Cell Line
  • Cell Proliferation
  • DNA, Complementary / genetics
  • DNA, Complementary / metabolism
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • RNA / genetics
  • RNA / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Tristetraprolin / genetics
  • Tristetraprolin / metabolism*
  • Zinc Fingers

Substances

  • DNA, Complementary
  • RNA-Binding Proteins
  • Tristetraprolin
  • ZFP36 protein, human
  • RNA