Abstract
BackgroundALDOA is a glycolytic enzyme found mainly in developing embryos, adult muscle and various malignant tumours, including pancreatic tumours. Our previous study revealed that ALDOA, an oncogene, can promote the proliferation and metastasis of pancreatic tumours. Furthermore, ALDOA could predict poor prognosis in patients with pancreatic tumours.MethodsIHC analysis of PDAC tissues was conducted. Western blotting, PCR, cellular IF experiments and cell cycle assessment were conducted utilizing cell lines. GSEA and KEGG pathway analysis were used to identify potential downstream pathways.ResultsTo explore the effects of ALDOA on the occurrence and development of pancreatic tumours, we analysed the RNA sequencing results and found that ALDOA could inhibit the DDR. Under normal circumstances, when DNA is damaged, initiation of the DDR causes cell cycle arrest, DNA repair or cell apoptosis. Further experiments showed that ALDOA could inhibit DNA repair and reverse cell cycle arrest induced by DNA damage so that DNA damage persisted to promote the occurrence and progression of cancer.ConclusionsRegarding the molecular mechanism, we found that ALDOA inhibited the DDR and improved activation of the cell cycle checkpoint PLK1 by suppressing ATM, which promotes tumour cell progression. Consequently, ALDOA has a profound effect on pancreatic cancer development.
Highlights
Because of the presence of most of typical symptoms only at the middle and late stages, local recrudesce and distant metastasis and a poor response to Fructose-bisphosphate aldolase A (ALDOA), a type of glycolytic enzyme, can catalyse reversibleChen et al Cancer Cell Int (2021) 21:514 conversion, which converts fructose-1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate [3]
ALDOA participated in the regulation of the cell cycle and the DNA damage response (DDR) By short hairpin RNA (shRNA)-mediated silencing with two shRNA constructs, we reduced ALDOA expression in the PANC-1 and SW1990 cell lines
To identify correlated pathways and genes, gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted, and the results revealed that ALDOA might be related to DNA repair (Fig. 1C and D)
Summary
Because of the presence of most of typical symptoms only at the middle and late stages, local recrudesce and distant metastasis and a poor response to Fructose-bisphosphate aldolase A (ALDOA), a type of glycolytic enzyme, can catalyse reversibleChen et al Cancer Cell Int (2021) 21:514 conversion, which converts fructose-1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate [3]. Our previous study indicated that ALDOA promoted the proliferation and metastasis of pancreatic cancer, partially through the regulation of E-cadherin expression, and predicted a dismal prognosis in patients with pancreatic cancer [7]. Ataxia telangiectasia mutated (ATM), the most upstream DDR kinase, is able to identify DNA damage, transmit DNA damage signals to downstream target proteins, activate stress systems, and induce cell cycle arrest [8,9,10]. Gaul conducted in vitro experiments and confirmed that bendamustine could induce G2 phase arrest by activating the ATM-Chk2-Cdc signalling pathway in myeloma cells [11]. Our previous study revealed that ALDOA, an oncogene, can promote the proliferation and metastasis of pancreatic tumours. ALDOA could predict poor prognosis in patients with pancreatic tumours
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