Significant association of PKM2 and NQO1 proteins with poor prognosis in breast cancer |
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| Affiliation: | 1. Cancer Research Center, Yanbian University Medical College, Yanji 133002, China;2. Department of Biochemistry and molecular biology, Yanbian University Medical College, Yanji 133002, China;3. Key laboratory of the Science and Technology Department of Jilin Province, Yanji 133002, China;1. Pathology Unit, Department of Advanced Biomedical Sciences, University of Naples “Federico II”, Naples, Italy;2. Gynecology and Obstetrics Unit, Department of Neurosciences, Reproductive Sciences and Dentistry, University of Naples “Federico II”, Naples, Italy;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia;2. Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt;3. Department of Anatomy, Mansoura Faculty of Medicine, Mansoura University, Egypt;4. Almaarefa University, College of Medicine, Riyadh, Saudi Arabia;5. Department of Pharmacology & Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia;6. Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt;1. Department of Orthopedic Surgery, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran;2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran;3. Department of Histology and Embryology, Air Force Medical University, No.169 Changle West Road, Xincheng, Xi''an, Shaanxi, 710032, China;4. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;5. Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran;6. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;7. Department of Orthopedics, Xi’an Children’s Hospital, No.69 Xijuyuan Lane, Lianhu, Xi’an, Shaanxi, 710003, China;8. Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;1. Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea;2. Department of Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea |
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| Abstract: | Pyruvate kinase M2 (PKM2) and NAD(P)H:quinone oxidoreductase-1 (NQO1) have been known to play significant functions in tumorigenesis and development. The association between PKM2 and NQO1 in breast cancer continues, however, to be unclear. In the present study, according to UALCAN and GEPIA database, the mRNA levels of PKM2 and NQO1 in breast primary tumor were significantly higher compared to normal breast tissue. Consonant with these findings, increased expression of both PKM2 and NQO1 were detected in clinical samples and BC cell lines. More importantly, consolidated high expression of NQO1 and PKM2 were obtained to be related with worse clinical stage, relapse, shorter relapse free survival (RFS), and poorer overall survival (OS) in human breast cancer. We subsequently found that knockdown of NQO1 reduced the protein level of PKM2 significantly. Moreover, deletion of PKM2 significantly reduced colony formation, migration and invasion of BC cells. A positive correlation between PKM2 and NQO1 expression was identified by immunohistochemical analyses of 108 specimens of breast cancer patients (rs = 0.60, P = 0.00). Finally, endogenous Co-IP demonstrated that PKM2 and NQO1 interact in breast cancer cells. The results of this study suggest that the correlation between NQO1 and PKM2 might play a critical role during breast tumourigenesis and serve as novel diagnostic biomarkers for breast cancer. |
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| Keywords: | Breast cancer Pyruvate kinase M2 NAD(P)H:quinone oxidoreductase-1 Prognosis |
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