Ribosomal protein S14 silencing inhibits growth of acute myeloid leukemia transformed from myelodysplastic syndromes via activating p53

Hematology. 2014 Jun;19(4):225-31. doi: 10.1179/1607845413Y.0000000127. Epub 2013 Nov 25.

Abstract

Objectives: Ribosomal protein S14 (RPS14) plays a key role in erythropoiesis and causes p53 activation in 5q- syndrome. However, the oncogenic potential of RPS14 is not understood in leukemia and high-risk myelodysplastic syndrome (MDS). Here, we investigated the changes of proliferation and apoptosis of SKM-1, an acute myeloid leukemia (MDS/AML) cell line transformed from MDS, and explored the role of RPS14 in them.

Methods: SKM-1 cells were transfected with recombined lentiviral vector shRPS14. Reverse-transcribed polymerase chain reaction and western blot assay were carried to detect the expression of RPS14 and p53. Cell proliferation was determined by MTT assay. Cell cycle and apoptosis were detected through flow cytometry.

Results: When compared with negative control, the proliferation rate of SKM-1 cells transfected with RPS14 hairpin siRNA dropped by 30%. Transfected SKM-1 cells presented with activation of p53. Transfection also arrested cells in G0/G1 phase and induced apoptosis, indicating that RPS14 is involved in the pathophysiology of MDS/AML.

Discussion: These findings indicate that partial silencing of RPS14 inhibits the proliferation of MDS/AML cells, and RPS14 may negatively regulate p53 activation in MDS/AML cells.

Keywords: Acute myeloid leukemia; Myelodysplastic syndrome; P53; Proliferation; RPS14; Suppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Leukemic*
  • Genetic Therapy
  • Humans
  • Leukemia, Myeloid, Acute / etiology
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Myelodysplastic Syndromes / complications
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / pathology
  • RNA Interference*
  • RNA, Small Interfering / genetics
  • Ribosomal Proteins / genetics*
  • Tumor Suppressor Protein p53 / genetics*
  • Up-Regulation

Substances

  • RNA, Small Interfering
  • Ribosomal Proteins
  • Tumor Suppressor Protein p53
  • ribosomal protein S14