Knockdown of FAM64A suppresses proliferation and migration of breast cancer cells

Breast Cancer. 2019 Nov;26(6):835-845. doi: 10.1007/s12282-019-00991-2. Epub 2019 Jul 1.

Abstract

Background: FAM64A is a mitotic regulator promoting cell metaphase-anaphase transition, and it is frequently reported to be highly expressed in cancer cells. However, the role of FAM64A in human breast cancer (BrC) is poorly studied.

Methods: The expression of FAM64A mRNA in BrC samples was determined by RT-qPCR assay and TCGA database mining. Kaplan-Meier plotter was used to analyze whether FAM64A expression impacted prognosis. Then, the expression of FAM64A was silenced using RNA interference. Cell-counting assay, colony formation assay and flow cytometry assay were conducted to detect proliferation; transwell migration assay, EMT-related proteins expression (E-cadherin, N-cadherin and vimentin), and EMT-related transcription factors mRNA expression (Snail, Twist, Slug) were conducted to evaluate the migration ability.

Results: FAM64A was highly expressed in human BrC samples, which was negatively associated with poor survival time. Analysis of FAM64A expression in BrC cell lines demonstrated that the expression of FAM64A was significantly correlated with the proliferation rate and migration ability of BrC cells. Indeed, knockdown of FAM64A suppressed the proliferation of MDA-MB-231 and MCF-7 cells. Importantly, we also found that silencing of FAM64A inhibited the migration of BrC cells via impeding epithelial-mesenchymal transition.

Conclusions: Our findings suggest that FAM64A plays an important role in the proliferation and migration of BrC cells, which might serve as a potential target for BrC treatment.

Keywords: Breast cancer; EMT; FAM64A; Migration; Proliferation.

MeSH terms

  • Antigens, CD / metabolism
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cadherins / metabolism
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kaplan-Meier Estimate
  • MCF-7 Cells
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism*
  • Prognosis
  • RNA Interference
  • Snail Family Transcription Factors / metabolism
  • Transfection
  • Twist-Related Protein 1 / metabolism
  • Vimentin / metabolism

Substances

  • Antigens, CD
  • CDH1 protein, human
  • CDH2 protein, human
  • Cadherins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • PIMREG protein, human
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • VIM protein, human
  • Vimentin