Inhibition of SOCS6 confers radioresistance in esophageal squamous cell carcinoma

Biochem Biophys Res Commun. 2021 Apr 23:550:92-98. doi: 10.1016/j.bbrc.2021.02.105. Epub 2021 Mar 6.

Abstract

Esophageal cancer is one of the most common cancer of the digestive system and radiotherapy is widely applied in advanced esophageal cancer treatment, however radioresistance (RR) is one of the major reasons for radiotherapy failure. There is limited knowledge on the mechanisms that cause RR, here we identify suppressors of cytokine signaling 6 (SOCS6) is a negative regulator of radioresistance in ESCC cells. SOCS6 deficiency in ESCC cells conferred radioresistance in vitro and in vivo by increasing radiation-induced G2/M arrest, DNA damage repair and inhibiting radiation-induced apoptosis. Moreover, the transcriptome sequencing analysis demonstrates that the transcription of SOCS6 was partially p53-dependent. Importantly we found that highly correlated SOCS6 and P53 express lower in RR esophageal cancer tissues compare with radiosensitive ones. Collectedly our study uncovers that SOCS6, as a downstream effector of p53, is a key regulator involved in the radioresistance of ESCC.

Keywords: Esophageal squamous cell carcinoma (ESCC); Radioresistance; Suppressors of cytokine signaling 6 (SOCS6); p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / radiation effects
  • Cell Line
  • DNA Damage / radiation effects
  • DNA Repair / radiation effects
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / radiotherapy*
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / radiotherapy*
  • G2 Phase Cell Cycle Checkpoints / radiation effects
  • Humans
  • M Phase Cell Cycle Checkpoints / radiation effects
  • Promoter Regions, Genetic / genetics
  • RNA Interference
  • Radiation Tolerance / genetics*
  • Radiation Tolerance / radiation effects*
  • Suppressor of Cytokine Signaling Proteins / biosynthesis
  • Suppressor of Cytokine Signaling Proteins / deficiency*
  • Suppressor of Cytokine Signaling Proteins / genetics*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • SOCS6 protein, human
  • Suppressor of Cytokine Signaling Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53