ArticleCell death & disease2020
Nonenzymatic function of Aldolase A downregulates miR-145 to promote the Oct4/DUSP4/TRAF4 axis and the acquisition of lung cancer stemness.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 36 citations in OpenAlex.
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- LncRNA ELFN1-AS1 maintains the stemness of colorectal cancer by preventing ubiquitinated degradation of the hnRNPA1 protein.Cellular and molecular life sciences : CMLS · 2026Article
- Aldolase a in pan-cancer and lung squamous cell carcinoma: prognostic value and macrophage-driven immune suppression unveiled by multi-omics and cohort validation.Cancer cell international · 2025Article
- Exploring the interplay between LDHA and ABCC1 in breast cancer using computational approach.Discover oncology · 2025Article
- Warburg effect and lactylation in cancer: mechanisms for chemoresistance.Molecular medicine (Cambridge, Mass.) · 2025Review
- Integrated multiomics machine learning and mediated Mendelian randomization investigate the molecular subtypes and prognosis lung squamous cell carcinoma.Translational lung cancer research · 2025Article
- [Comprehensive Analysis of the Expression, Prognosis and Function of TRAF Family Proteins in NSCLC].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Article
- Lnc-EST885 promotes hepatocellular carcinoma metastasis through PI3K / AKT pathway by interaction with TRAF4.Translational oncology · 2025Article
- The multifaceted roles of aldolase A in cancer: glycolysis, cytoskeleton, translation and beyond.Human cell · 2025Review
- The Intricate Web of MicroRNAs in Modulating EGFR-TKI Resistance in Non-Small Cell Lung Cancer: A Comprehensive Review.Cancer management and research · 2025Review
- Prognostic Significance of R-Loops in Lung Adenocarcinoma: Implications for Immune Response and Drug Sensitivity.Cancer management and research · 2025Article
- The Expression and Clinical Significance of ALDOA in Breast Cancer.OncoTargets and therapy · 2025Article
- The impact of epithelial-mesenchymal transition (EMT) induced by metabolic processes and intracellular signaling pathways on chemo-resistance, metastasis, and recurrence in solid tumors.Cell communication and signaling : CCS · 2024Review
- The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities.Neoplasia (New York, N.Y.) · 2024Review
- Diverse roles of aldolase enzymes in cancer development, drug resistance and therapeutic approaches as moonlighting enzymes.Medical oncology (Northwood, London, England) · 2024Review
- MicroRNA-142-3p chemo-sensitizing breast cancer to docetaxel: apoptosis and cell cycle arrest induction, and migration suppression.Veterinary research forum : an international quarterly journal · 2024Article
- Emerging roles of small extracellular vesicles in metabolic reprogramming and drug resistance in cancers.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Oncogenic Alterations of Metabolism Associated with Resistance to Chemotherapy.Current molecular medicine · 2024Review
- Aldolase A Accelerates Cancer Progression by Modulating mRNA Translation and Protein Biosynthesis via Noncanonical Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Aldolase A Promotes Colorectal Cancer Progression through Targeting COPS6 and Regulating MAPK Signaling Pathway.Disease markers · 2023Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug resistance remains a serious issue of clinical importance and is a consequence of cancer stemness. In this study, we showed that the level of Aldolase A (ALDOA) expression is significantly associated with the IC50 value of chemotherapy drugs in lung cancer. Our data revealed that ALDOA overexpression resulted in a significant increase of lung tumor spheres. The use of ingenuity pathway analysis (IPA) resulted in the identification of POU5F1 (Oct4) as the leading transcription factor of ALDOA. We observed high expression of ALDOA, Oct4 and stemness markers in collected spheroid cells. DUSP4 and TRAF4 were confirmed as major downstream targets of the ALDOA-Oct4 axis. Knockdown of these molecules significantly decreased the stemness ability of cells. In addition, we investigated whether miR-145 targets the 3'-UTR of Oct4 and is regulated by ALDOA due to the involvement of ALDOA in glycolysis and metabolic reprogramming. Furthermore, we constructed several mutant forms of ALDOA that disrupted its enzymatic activity and showed that they still induced significant in vitro sphere formation and in vivo tumorigenicity. These results demonstrated that ALDOA-mediated spheroid formation is independent of its enzymatic activity. In the clinical component, we also showed that the combination of ALDOA and TRAF4 or DUSP4 is positively correlated with poor overall survival in a xenograft model and cancer patients through immunohistochemical analyses. The results of our study revealed novel functional roles of ALDOA in inducing cancer stemness via the inhibition of miR-145 expression and the activation of Oct4 transcription. These findings offer new therapeutic strategies for modulation of lung cancer stemness to enhance chemotherapeutic responses in lung cancer patients.
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