Silencing FAM135B enhances radiosensitivity of esophageal carcinoma cell

Gene. 2021 Mar 10:772:145358. doi: 10.1016/j.gene.2020.145358. Epub 2020 Dec 17.

Abstract

FAM135B (family with sequence similarity 135, member B) is related to the progression of esophageal squamous cell carcinoma (ESCC). However, the role played by the gene in radiosensitivity remains unknown. Herein, we examined the relationship between FAM135B and radiosensitivity. According to the results, FAM135B is highly expressed in ESCC cells, and ESCC cells with high levels of FAM135B are resistant to irradiation. Silencing FAM135B inhibits colony formation capability and cell cycle protein expression (pP53, CDK1), promotes cell cycle arrest at the G2/M phase following irradiation. Moreover, transcriptome sequencing analysis demonstrates that FAM135B regulates downstream PI3K/Akt/mTOR signaling pathway, and western blot verifies the result. One of the mechanisms of increasing radiosensitivity by silencing FAM135B expression in ESCC cells may be achieved by regulating the PI3K/Akt/mTOR signaling pathway. Silencing FAM135B shows synergy with PI3K/Akt/mTOR pathway inhibitor (rapamycin) in increasing radiosensitivity, regulating the expression of cell cycle protein and inducing apoptosis of ESCC cells. The results indicate that FAM135B could be a potential treatment target for ESCC in management of radiosensitivity.

Keywords: Apoptosis; Esophageal squamous cell carcinoma; Family with sequence similarity 135, member B; Radiosensitivity; Transcriptome sequencing.

MeSH terms

  • Cell Cycle / drug effects
  • Cell Cycle / radiation effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / therapy
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / therapy
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Gene Silencing
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • RNA, Small Interfering / pharmacology*
  • Radiation Tolerance / drug effects
  • Signal Transduction / drug effects
  • Signal Transduction / radiation effects
  • Sirolimus / pharmacology
  • Up-Regulation / drug effects*

Substances

  • FAM135B protein, human
  • Intracellular Signaling Peptides and Proteins
  • RNA, Small Interfering
  • Sirolimus