USP12 promotes nonsmall cell lung cancer progression through deubiquitinating and stabilizing RRM2

Author:

Chen Congcong12,Xue Ning3,Liu Kangshou12,He Qiang2,Wang Cong4,Guo Yanguan12,Tian Jiaxin2,Liu Xinjian5,Pan Yunlong1,Chen Guo24

Affiliation:

1. Department of General Surgery The First Affiliated Hospital of Jinan University Guangzhou P.R. China

2. Department of Medical Biochemistry and Molecular Biology, School of Medicine Jinan University Guangzhou P.R. China

3. Department of Acupuncture Jurong Hospital Affiliated to Jiangsu University Zhenjiang P.R. China

4. School of Biopharmacy China Pharmaceutical University Nanjing P.R. China

5. Department of Pathogen Biology, Key Laboratory of Antibody Technique of National Health Commission of China Nanjing Medical University Nanjing P.R. China

Abstract

AbstractRRM2 is the catalytic subunit of ribonucleotide reductase (RNR), which catalyzes de novo synthesis of deoxyribonucleotide triphosphates (dNTPs) and plays critical roles in cancer cell proliferation. RRM2 protein level is controlled by ubiquitination mediated protein degradation system; however, its deubiquitinase has not been identified yet. Here we showed that ubiquitin‐specific peptidase 12 (USP12) directly interacts with and deubiquitinates RRM2 in non‐small cell lung cancer (NSCLC) cells. Knockdown of USP12 causes DNA replication stress and retards tumor growth in vivo and in vitro. Meanwhile, USP12 protein levels were positively correlated to RRM2 protein levels in human NSCLC tissues. In addition, high expression of USP12 was associated with poor prognosis in NSCLC patients. Therefore, our study reveals that USP12 is a RRM2 regulator and targeting USP12 could be considered as a potential therapeutical strategy for NSCLC treatment.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Subject

Cancer Research,Molecular Biology

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