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

Abstract

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.

Identification of core genes associated with prostate cancer progression and outcome via bioinformatics analysis in multiple databases

“…GNRH_signaling_pathway DNA_replication Cell_cycle elevated Cyclin B1 levels served as a biomarker for the prognosis of prostate cancer patients who were being treated with chemotherapy (Gomez et al, 2007). Ribonucleotide reductase regulatory subunit M2 (RRM2) is an enzyme that limits the rate of DNA synthesis and repair (Li et al, 2018;Wu et al, 2018). Mostly, RRM2 was overexpressed in PCa patients with a high Gleason score and an advanced T stage.…”

Independent prognostic implications of RRM2 in lung adenocarcinoma

“…Li et al illustrated that RRM2 was overexpressed in human glioblastoma cells, and promoted proliferation, migration, and invasion of human glioblastoma cells 34 . Suppression of RRM2 inhibits cell proliferation, causes cell cycle arrest, and promotes the apoptosis of human neuroblastoma cells 35 . In our story, the investigation of differential expression in LUAD found that RRM2 was highly expressed in tumor tissues, which was subsequently examined in multiple independent cohorts.…”

Potential mechanism of RRM2 for promoting Cervical Cancer based on weighted gene co-expression network analysis

“…International Publisher adrenocortical cancer [8], lung cancer [9], nasopharyngeal cancer [10], gastric cancer [11] and neuroblastoma [12], as well as being a predictor of poor prognosis [13][14][15][16][17]. Our previous study had indicated that RRM2 plays a critical role in the diagnosis and treatment of cervical cancer [18].…”