Aldolase B impairs DNA mismatch repair and induces apoptosis in colon adenocarcinoma

Jiabian Lian; Lu Xia; Yixing Chen; Jiani Zheng; Ke Ma; Lingtao Luo; Feng Ye

doi:10.1016/j.prp.2019.152597

Aldolase B impairs DNA mismatch repair and induces apoptosis in colon adenocarcinoma

Pathol Res Pract. 2019 Nov;215(11):152597. doi: 10.1016/j.prp.2019.152597. Epub 2019 Aug 16.

Authors

Jiabian Lian¹, Lu Xia¹, Yixing Chen², Jiani Zheng³, Ke Ma⁴, Lingtao Luo⁵, Feng Ye⁶

Affiliations

¹ Laboratory of Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China; Department of Clinical Medical, Fujian Medical University, Fuzhou, China; Department of Cancer Prevention Diagnosis and Treatment, Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China.
² Laboratory of Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China; Department of Clinical Medical, Fujian Medical University, Fuzhou, China.
³ Department of Medical Oncology, Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China; Department of Clinical Medical, Fujian Medical University, Fuzhou, China; Department of Cancer Prevention Diagnosis and Treatment, Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China.
⁴ Department of Gastrointestinal Surgery, Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China.
⁵ Department of Gastrointestinal Surgery, Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China; Department of Clinical Medical, Fujian Medical University, Fuzhou, China; Department of Cancer Prevention Diagnosis and Treatment, Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China. Electronic address: luolingtao8711@163.com.
⁶ Department of Medical Oncology, Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China; Department of Clinical Medical, Fujian Medical University, Fuzhou, China; Department of Cancer Prevention Diagnosis and Treatment, Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China. Electronic address: yefengdoctor@xmu.edu.cn.

PMID: 31564566
DOI: 10.1016/j.prp.2019.152597

Abstract

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.

Keywords: Aldolase B; Apoptosis; Colon adenocarcinoma; MMR; Prognosis.

MeSH terms

Adenocarcinoma / enzymology*
Adenocarcinoma / pathology*
Apoptosis / physiology
Colonic Neoplasms / enzymology*
Colonic Neoplasms / pathology*
DNA Mismatch Repair / physiology*
Fructose-Bisphosphate Aldolase / metabolism*
Humans
Microsatellite Instability

Substances

Fructose-Bisphosphate Aldolase