Downregulation of RPS14 inhibits the proliferation and metastasis of estrogen receptor-positive breast cancer cells

Anticancer Drugs. 2021 Nov 1;32(10):1019-1028. doi: 10.1097/CAD.0000000000001112.

Abstract

Ribosomal protein S14 (RPS14) is a component of the 40S ribosomal subunit and is considered to be indispensable for ribosomal biogenesis. Previously, we found that RPS14 was significantly downregulated in estrogen receptor-positive (ER+) breast cancer cells following treatment with 4-hydroxytamoxifen (4-OH-TAM). However, its role in breast cancer remains poorly understood. In the present study, we sought to demonstrate, for the first time, that RPS14 is highly expressed in ER+ breast cancer tissues and its downregulation can significantly inhibit the proliferation, cycle, and metastasis of ER+ breast cancer cells, as well as induce cell apoptosis. Quantitative RT-PCR and western blotting were used to determine the expression of target genes. Herein, lentivirus-mediated small hairpin RNA (shRNA) targeting RPS14 was designed to determine the impact of RPS14 knockdown on ER+ breast cancer cells. Further, bioinformatics analysis was used to reveal the significance of differentially expressed genes in RPS14 knockdown breast cancer cells. RPS14 was highly expressed in ER+ breast cancer tissues compared to ER- tissues. The downregulation of RPS14 in two ER+ breast cancer cell lines suppressed cell proliferation, cell cycle and metastasis, and induced apoptosis. Based on bioinformatics analysis, the expression level of several significant genes, such as ASNS, Ret, and S100A4, was altered in breast cancer cells after RPS14 downregulation. Furthermore, the BAG2 and interferon signaling pathways were identified to be significantly activated. The downregulation of RPS14 in ER+ breast cancer cells can inhibit their proliferation and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Breast Neoplasms / pathology*
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interferons / drug effects
  • Neoplasm Metastasis
  • RNA, Small Interfering / pharmacology*
  • Receptors, Estrogen / biosynthesis*
  • Ribosomal Proteins / drug effects*
  • Signal Transduction / drug effects

Substances

  • RNA, Small Interfering
  • Receptors, Estrogen
  • Ribosomal Proteins
  • ribosomal protein S14
  • Interferons