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.
Keywords:
CRC; HIF-1α; RPS7; glycolysis; proliferation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Adenocarcinoma / prevention & control*
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Adenocarcinoma, Mucinous / metabolism
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Adenocarcinoma, Mucinous / pathology
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Adenocarcinoma, Mucinous / prevention & control*
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Adult
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Aged
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Animals
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Apoptosis
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Cell Proliferation
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Colorectal Neoplasms / metabolism
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Colorectal Neoplasms / pathology
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Colorectal Neoplasms / prevention & control*
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Female
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Glucose Transporter Type 4 / genetics
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Glucose Transporter Type 4 / metabolism
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Glycolysis*
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
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Immunoenzyme Techniques
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Lactate Dehydrogenases / genetics
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Lactate Dehydrogenases / metabolism
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Middle Aged
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Neoplasm Grading
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Neoplasm Staging
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Prognosis
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Ribosomal Proteins / genetics
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Ribosomal Proteins / metabolism*
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Signal Transduction
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Survival Rate
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Tumor Cells, Cultured
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Xenograft Model Antitumor Assays
Substances
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Glucose Transporter Type 4
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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RNA, Messenger
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Ribosomal Proteins
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SLC2A4 protein, human
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ribosomal protein S7
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Lactate Dehydrogenases
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D-lactate dehydrogenase