Aldolase B impairs DNA mismatch repair and induces apoptosis in colon adenocarcinoma
| Autor: | Feng Ye, Luo Lingtao, Xia Lu, Yixing Chen, Lian Jiabian, Jiani Zheng, Ke Ma |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway DNA repair DNA damage Apoptosis Adenocarcinoma DNA Mismatch Repair Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Fructose-Bisphosphate Aldolase medicine Humans biology Aldolase B Microsatellite instability Cell Biology Base excision repair medicine.disease digestive system diseases 030104 developmental biology 030220 oncology & carcinogenesis Colonic Neoplasms biology.protein Cancer research DNA mismatch repair Microsatellite Instability |
| Zdroj: | Pathology, research and practice. 215(11) |
| ISSN: | 1618-0631 |
| Popis: | Evidence suggests that DNA repair capacity manifested by intact functional base excision repair and mismatch repair (MMR) pathways is related to the prognosis of multiple cancer types. Aldolase B (ALDOB) is well known for its role in metabolism and glycolysis. The expression of ALDOB in colon adenocarcinoma and the relationship between its expression and colon adenocarcinoma prognosis remain controversial; in addition, the potential role of ALDOB in DNA MMR has not yet been reported. In this study, we identified a cluster of DNA repair-related proteins that interact with ALDOB in the colon adenocarcinoma cell line HCT116. Expression analysis of colon adenocarcinoma data from the Cancer Genome Atlas (TCGA-COAD data, n = 551) indicated that ALDOB mRNA expression was significantly higher in specimens with microsatellite instability (MSI) than in specimens with microsatellite stability (MSS). Regarding prognosis, colon adenocarcinoma patients with high ALDOB mRNA expression had longer overall survival (OS). Higher expression of ALDOB protein was significantly correlated with MMR deficiency (d-MMR) in formalin-fixed paraffin-embedded (FFPE) patient specimens. The expression of ALDOB was significantly elevated in colon adenocarcinoma cell lines. Further evidence indicated that rather than affecting proliferation, ALDOB overexpression induced the functional loss of MMR proteins and in turn caused irreversible DNA damage via disrupting EZH2-Rad51 expression and then caused apoptosis by ERK inactivation. Overall, our study demonstrates that high ALDOB expression impairs DNA MMR and induces apoptosis in colon adenocarcinoma. ALDOB may be a new biomarker associated with d-MMR and an independent prognostic factor for colon adenocarcinoma. |
| Databáze: | OpenAIRE |
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