Downregulated RRS1 inhibits invasion and metastasis of BT549 through RPL11‑c‑Myc‑SNAIL axis

Int J Oncol. 2022 Mar;60(3):33. doi: 10.3892/ijo.2022.5323. Epub 2022 Feb 18.

Abstract

Regulator of ribosome synthesis 1 (RRS1) is a key factor in ribosome biosynthesis and other cellular functions. High level of RRS1 in breast cancer cell lines is associated with increased cell proliferation, invasion and migration. RRS1 controls the assembly of the 60s subunit and maturation of 25S rRNA during ribosome biosynthesis. In this study, lentiviral transfection of sh‑RNA was used to knock down the level of RRS1, to detect the effect of RRS1 on cell function and to explore the specific mechanism of RRS1 affecting cell invasion and metastasis by COIP and dual‑luciferase reporter gene assays. The present study found that RRS1 knockdown reduced the accumulation of ribosome protein L11 (RPL11) in the nucleolus, which then migrated to the nucleoplasm and bound to c‑Myc. This inhibited trans‑activation of SNAIL by c‑Myc and eventually decreased the invasion and metastasis capacity of the human breast cancer cell line BT549. Taken together, RRS1 regulates invasion and metastasis of human breast cancer cells through the RPL11‑c‑Myc‑SNAIL axis. The findings are of great significance for exploring the mechanism of breast cancer invasion and metastasis and the corresponding regulatory factors.

Keywords: breast cancer; invasion and metastasis; regulator of ribosome synthesis 1; ribosome biosynthesis; ribosome protein L11.

MeSH terms

  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / metabolism
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / genetics
  • Down-Regulation / drug effects
  • Down-Regulation / genetics*
  • Humans
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / prevention & control
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / drug effects*
  • RNA-Binding Proteins / genetics
  • Snail Family Transcription Factors / drug effects
  • Snail Family Transcription Factors / genetics
  • Transcription Factors / drug effects
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • MYCBP protein, human
  • RNA-Binding Proteins
  • RRS1 protein, human
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors

Grants and funding

The present study was supported by the National Natural Science Foundation of China (grant no. 81472542) and Chinese Medicine Projects in Shandong Province (grant no. 2021Z036).