RBM3 upregulates ARPC2 by binding the 3'UTR and contributes to breast cancer progression

Int J Oncol. 2019 Apr;54(4):1387-1397. doi: 10.3892/ijo.2019.4698. Epub 2019 Jan 28.

Abstract

Breast cancer is one of the most common types of cancers which results in a high mortality rate for patients worldwide. In this study, we performed systematical experiments including tissue analysis (immunohistochemistry etc.) and cell functional experiments (cell counting assay, MTT assay, cell colony formation, cell migration assay, cell invasion assay etc.). We demonstrated that the expression level of RNA binding motif protein 3 (RBM3) was higher in human breast cancer tissues compared with adjacent non‑tumor tissues. A high level of RBM3 was associated with worse post‑operative relapse‑free survival (RFS) and overall survival (OS) rates in patients with breast cancer. Among the patients with breast cancer, the expression of RBM3 was associated with patient lymph node metastasis and a high tumor grade. The knockdown of RBM3 markedly decreased the proliferation and metastasis of human breast cancer cells. In downstream pathway analysis, actin related protein 2/3 complex subunit 2 (ARPC2) was determined to be positively regulated by RBM3 through a post‑transcriptional 3'UTR‑binding manner. ARPC2 also played an oncogenic role and mediated the promoting role of RBM3 in the proliferation and metastasis of human breast cancer cells. Thus, on the whole, the findings of this study demonstrate that RBM3 acts as an oncogene in human breast cancer cells and that the functional depletion of RBM3 may be considered as a potential method for breast cancer therapy.

Keywords: RNA binding motif protein 3; actin related protein 2/3 complex subunit 2; proliferation; metastasis; breast cancer.

MeSH terms

  • 3' Untranslated Regions
  • Actin-Related Protein 2-3 Complex / genetics*
  • Actin-Related Protein 2-3 Complex / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Neoplasm Grading
  • Neoplasm Metastasis
  • RNA-Binding Proteins / metabolism*
  • Survival Analysis
  • Up-Regulation*

Substances

  • 3' Untranslated Regions
  • ARPC2 protein, human
  • Actin-Related Protein 2-3 Complex
  • RBM3 protein, human
  • RNA-Binding Proteins