Research Papers:
RPS7 inhibits colorectal cancer growth via decreasing HIF-1α-mediated glycolysis
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Abstract
Wen Zhang1,*, Duo Tong1,4,*, Fei Liu2,4,*, Dawei Li3, Jiajia Li2,4, Xi Cheng2,4, Ziliang Wang1,2,4
1Cancer Institute and Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
2Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
3Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
4Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
*These authors contributed equally to this work
Correspondence to:
Wen Zhang, e-mail: [email protected]
Ziliang Wang, e-mail: [email protected]
Keywords: RPS7, HIF-1α, glycolysis, proliferation, CRC
Received: September 21, 2015 Accepted: December 09, 2015 Published: December 31, 2015
ABSTRACT
Ribosomal protein S7 (RPS7) acts as a tumor suppressor in primary tumorigenesis but its role in cancer metabolism remains unclear. In this study, we demonstrate that RPS7 inhibits the colorectal cancer (CRC) cell glycolysis by suppressing the expression of hypoxia-inducible transcription factor-1α (HIF-1α) and the metabolic promoting proteins glucose transporter 4 (GLUT4) and lactate dehydrogenase B (LDHB). Further study found that the enhanced expression of HIF-1α abrogates the overexpression effects of RPS7 on CRC. In vivo assays also demonstrate that RPS7 suppresses colorectal cancer tumorigenesis and glycolysis. Clinically, the tissue microarray (TMA) analysis discloses the negative regulatory association between RPS7 and HIF-1α in colorectal cancer. Meanwhile, overexpression of RPS7 in colorectal cancer tissues predicts good overall survival and progression-free survival, but high expression level of HIF-1α indicates poor overall survival and progression-free survival. Overall, we reveal that RPS7 inhibits colorectal cancer glycolysis through HIF-1α-associated signaling and may be a promising biomarker for prognosis prediction and a potential target for therapeutic treatment.
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