Suppression of RRM2 inhibits cell proliferation, causes cell cycle arrest and promotes the apoptosis of human neuroblastoma cells and in human neuroblastoma RRM2 is suppressed following chemotherapy

Oncol Rep. 2018 Jul;40(1):355-360. doi: 10.3892/or.2018.6420. Epub 2018 May 8.


Ribonucleotide reductase regulatory subunit M2 (RRM2) is a rate‑limiting enzyme for DNA synthesis and repair. RRM2 has vital roles in controlling the progression of cancer. In the present study, we investigated the RRM2 level in neuroblastoma tissues, analyzed its relationship with clinicopathological characteristics of neuroblastoma patients, and explored the effect of RRM2 on the biological functions of neuroblastoma cells. RRM2 levels in 67 pairs of neuroblastoma and matched adjacent non‑cancerous tissues were detected by qRT‑PCR, and its association with patient clinicopathological features was assessed. Using RRM2 siRNA, the role of RRM2 in cell viability was detected by CCK‑8 assay, and the effects on cell cycle distribution and cell apoptosis were detected by flow cytometry. Hoechst 33342 staining was also performed. For RRM2 protein detection in cells and tissues, western blot analyses were employed. Our results revealed that RRM2 expression was significant higher in neuroblastoma tissues than that noted in adjacent non‑cancerous tissues at both the mRNA and protein levels. The increased RRM2 level was significantly associated with clinical stage. RRM2 levels were suppressed in stage III and IV tumors in the chemotherapy subgroup, compared with levels noted in tumors in the preoperative non‑chemotherapy subgroup. RRM2 siRNA significantly inhibited cell viability in the SH‑5Y5Y cells, induced cell arrest in the G0/G1 phase, and enhanced cell apoptosis. Taken together, overexpression of RRM2 is associated with the genesis and progression of neuroblastoma, and may be a potential chemotherapeutic target.

MeSH terms

  • Adolescent
  • Apoptosis / drug effects
  • Biomarkers, Tumor / genetics*
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Infant
  • Male
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / genetics*
  • Neuroblastoma / pathology
  • Neuroblastoma / surgery
  • Preoperative Care
  • RNA, Small Interfering / pharmacology
  • Ribonucleoside Diphosphate Reductase / antagonists & inhibitors
  • Ribonucleoside Diphosphate Reductase / genetics*


  • Biomarkers, Tumor
  • RNA, Small Interfering
  • ribonucleotide reductase M2
  • Ribonucleoside Diphosphate Reductase