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Ribonucleotide reductase subunit M2 as a novel target for clear-cell renal cell carcinoma
- Source :
- OncoTargets and Therapy. 12:3267-3275
- Publication Year :
- 2019
- Publisher :
- Informa UK Limited, 2019.
-
Abstract
- Background: Sufficient supply of deoxyribonucleoside triphosphates (dNTPs) is required for the uncontrolled replication of cancers. The current study aimed to investigate the biological and clinical role of ribonucleotide reductase subunit M2 (RRM2), a key enzyme regulating the dNTP pool, in clear-cell renal cell carcinoma (ccRCC). Methods: The expression of RRM2 on disease progression and patient outcome was assessed in ccRCC. Then, the effect of RRM2 inhibition on renal cell carcinoma (RCC) growth using siRNA or Triapine, an RRM2-specific inhibitor, was characterized in RCC cell lines. Results: The expression of RRM2 was up-regulated in ccRCC tissues as compared to the normal tissues. Patients with high RRM2 expression tend to have advanced pT stages, high Fuhrman grades, and shortened overall survival (OS). RRM2-siRNAs or Triapine significantly inhibited the cell growth by inducing G0/G1 cell cycle arrest in RCC cells through the attenuation of dNTP pool. Conclusions: The current results provided evidence that RRM2 might act as a novel target for ccRCC, and exploration of nonnucleoside, reversible, small-molecule inhibitors against RRM2 could be promising.
- Subjects :
- 0301 basic medicine
Cell growth
medicine.medical_treatment
medicine.disease
Targeted therapy
Deoxyribonucleoside
03 medical and health sciences
chemistry.chemical_compound
Clear cell renal cell carcinoma
030104 developmental biology
0302 clinical medicine
Oncology
chemistry
Renal cell carcinoma
Cell culture
030220 oncology & carcinogenesis
medicine
Cancer research
Pharmacology (medical)
Ribonucleotide Reductase Subunit
G1 phase
Subjects
Details
- ISSN :
- 11786930
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- OncoTargets and Therapy
- Accession number :
- edsair.doi...........822768c2ff3869857d4b33b49bf1fefb