Elevated transcriptional levels of aldolase A (ALDOA) associates with cell cycle-related genes in patients with NSCLC and several solid tumors

Abstract

BackgroundAldolase A (ALDOA) is one of the glycolytic enzymes primarily found in the developing embryo and adult muscle. Recently, a new role of ALDOA in several cancers has been proposed. However, the underlying mechanism remains obscure and inconsistent. In this study, we tried to investigate ALDOA-associated (AA) genes using available microarray datasets to help elucidating the role of ALDOA in cancer.ResultsIn the dataset of patients with non-small-cell lung cancer (NSCLC, E-GEOD-19188), 3448 differentially expressed genes (DEGs) including ALDOA were identified, in which 710 AA genes were found to be positively associated with ALDOA. Then according to correlation coefficients between each pair of AA genes, ALDOA-associated gene co-expression network (GCN) was constructed including 182 nodes and 1619 edges. 11 clusters out of GCN were detected by ClusterOne plugin in Cytoscape, and only 3 of them have more than three nodes. These three clusters were functionally enriched. A great number of genes (43/79, 54.4%) in the biggest cluster (Cluster 1) primarily involved in biological process like cell cycle process (P a = 6.76E-26), mitotic cell cycle (P a = 4.09E-19), DNA repair (P a = 1.13E-04), M phase of meiotic cell cycle (P a = 0.006), positive regulation of ubiquitin-protein ligase activity during mitotic cell cycle (P a = 0.014). AA genes with highest degree and betweenness were considered as hub genes of GCN, namely CDC20, MELK, PTTG1, CCNB2, CDC45, CCNB1, TK1 and PSMB2, which could distinguish cancer from normal controls with ALDOA. Their positive association with ALDOA remained after removing the effect of HK2 and PKM, the two rate limiting enzymes in glycolysis. Further, knocking down ALDOA blocked breast cancer cells in the G0/G1 phase under minimized glycolysis. All suggested that ALDOA might affect cell cycle progression independent of glycolysis. RT-qPCR detection confirmed the relationship of ALDOA with CDC45 and CCNB2 in breast tumors. High expression of the hub genes indicated poor outcome in NSCLC. ALDOA could improve their predictive power.ConclusionsALDOA could contribute to the progress of cancer, at least partially through its association with genes relevant to cell cycle independent of glycolysis. AA genes plus ALDOA represent a potential new signature for development and prognosis in several cancers.

Aldolase A promotes proliferation and G1/S transition via the EGFR/MAPK pathway in non‐small cell lung cancer

“…In the present study, we found that ALDOA knockdown resulted in G 1 /S blockage. Similarly, previous bioinformatics analysis results suggest a correlation between ALDOA and the cell cycle in NSCLC [ 47 ]. These results imply that ALDOA plays a role in the occurrence of NSCLC and is a potential early marker of NSCLC.…”

Aldolase A as a prognostic factor and mediator of progression via inducing epithelial–mesenchymal transition in gastric cancer

“…In the pancreas, it promotes tumorigenesis and progression into a highly metastatic pancreatic cancer by regulating the expression of E‐cadherin . It regulates the cell cycle in non‐small cell lung cancer and several solid tumours …”

C/D-Box Snord105b Promotes Tumorigenesis in Gastric Cancer via ALDOA/C-Myc Pathway

“…ALDOA, which is a highly conserved gene among different species and a well-studied member of the aldolase family, has been reported to be upregulated in various types of tumor cells, including oral squamous cell carcinoma, osteosarcoma, hepatocellular carcinoma and lung cancer [22-26]. Du et al found that ALDOA might promote the progression of lung cancer through EMT [27].…”