FAM98A associates with DDX1-C14orf166-FAM98B in a novel complex involved in colorectal cancer progression

Int J Biochem Cell Biol. 2017 Mar;84:1-13. doi: 10.1016/j.biocel.2016.12.013. Epub 2016 Dec 28.

Abstract

Protein Arginine Methyl Transferase 1 (PRMT1) is deemed to be a potential oncogenic protein considering its overexpression in several malignancies including colorectal cancer. However, the molecular pathogenesis regarding PRMT1 overexpression and overall poor patient survival involved in this devastating and life threatening cancer remains obscured. In our previous study, we have identified FAM98A as a novel substrate of PRMT1 and also identified its role in ovarian cancer progression. Here, we showed that the two structural homologs FAM98A and FAM98B included in a novel complex with DDX1 and C14orf166 are required for PRMT1 expression. Analysis of the data from The Cancer Genome Atlas (TCGA) database and clinical colorectal cancer specimens also demonstrated a strong positive correlation and co-occurrence of PRMT1, FAM98A and FAM98B. These findings provide a mechanistic insight into how knockdown of FAM98A or FAM98B can suppress the malignant characteristics of cancer cells. Besides, we showed that FAM98A and FAM98B are working in the same axis as knockdown of both proteins together does not cause additional reduction in the cellular proliferation and colony formation of colorectal cancer cells.

Keywords: Colorectal cancer; FAM98A; FAM98B; PRMT1.

MeSH terms

  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Proliferation
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • DEAD-box RNA Helicases / metabolism*
  • Disease Progression
  • Gene Knockdown Techniques
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Multiprotein Complexes / metabolism
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / metabolism*
  • Proteins / antagonists & inhibitors
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Trans-Activators / metabolism*
  • Tumor Stem Cell Assay

Substances

  • Carrier Proteins
  • FAM98A protein, human
  • FAM98B protein, human
  • Multiprotein Complexes
  • Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • RTRAF protein, human
  • Repressor Proteins
  • Trans-Activators
  • PRMT1 protein, human
  • Protein-Arginine N-Methyltransferases
  • DDX1 protein, human
  • DEAD-box RNA Helicases