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.
Highlights
Colorectal cancer (CRC) is one of the most common cancers worldwide, ranking the third of the leading causes of cancer death [1]
We introduced retroviruses carrying short hairpin RNA (shRNA) against Ribosomal protein S7 (RPS7) into HT29 and LOVO cells to generate HT29/RPS7 shRNA LOVO/ RPS7 shRNA cells
We found that the nuclear score for RPS7 was negatively correlated with hypoxia-inducible transcription factor-1α (HIF-1α), glucose transporter 4 (GLUT4) or lactate dehydrogenase B (LDHB) staining in tumor tissues (p < 0.05), evidenced by the representative images showing the high expression of RPS7 corresponding to the low expressions of HIF1α, GLUT4 or LDHB in same tissues (Figure 5A), or vice versa (Figure 5B)
Summary
Colorectal cancer (CRC) is one of the most common cancers worldwide, ranking the third of the leading causes of cancer death [1]. Traditional TNM (T, tumor; N, lymph node; M, metastasis) staging system provides important information for predicting prognosis, while even with the same stage some CRC show worse biological behaviors. Some RPs promote the process of oncogenesis, such as silencing of RPS13 restrains the growth of gastric cancer [8] and down-regulation of RPL6 inhibits the proliferation of gastric cancer [9]. Parts of RPs have the potential to be prognostic or diagnostic markers in various cancers, for instance increased RPL13 expression has been found to be positively correlated with clinical staging of gastric cancers [13], and low expression of RPS4 is associated with poor prognosis in ovarian cancer [14]. The exact role of RPs in cancers and their underlying mechanisms still remain largely unknown
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