Document Type : Research Articles
Authors
1
Department of Biosciences, Manipal University Jaipur, Dehmi Kalan, Jaipur-Ajmer Expressway, Jaipur, Rajasthan, 303007, India.
2
Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Bhopal, Saket Nagar, Bhopal 462020, Madhya Pradesh, India.
Abstract
Objective: Lactate dehydrogenase is dysregulated in several cancer types. However, the mechanism of its dysregulation in lung cancer is not fully understood. We utilized web-based computational databases to conduct gene expression analysis on LDHA, identified its regulator, and explored their role in the prognosis of lung cancer. Methods: We used various web-based computational tools, including the UALCAN, TIMER2.0, ENCORI, TCGA Portal, OncoDB, and GEPIA2 datasets for lung cancer analysis in this study. We also performed survival, biological processes, and metastasis analysis using various computational tools. We also carried out co-expression functional enrichment analysis using the Enrichr and TIMER databases, multivariate analysis of survival and pathological stage, and transcriptional regulation analysis using the ENCORI and OncoDB datasets. Furthermore, LDHA inhibitor binding of withanolides was analyzed using Auto Dock Tools 1.5.6, LigPlot+, and Pymol. Results: The study found that the higher levels of LDHA gene expression were associated with poor prognosis and overall survival in lung cancer patients. We identified 11 key genes co-expressed with LDHA; out of them, two genes, MKI67 and PGK1, showed a strong positive correlation with LDHA and associated poor survival outcomes in LUAD patients. Furthermore, we also identified hsa-let-7c-5p and TMPO-AS1 as potential regulators of LDHA in LUAD. It might be possible that the TMPO-AS1- hsa-let-7c-5p-LDHA ceRNA network could serve as a potential regulator of aerobic glycolysis in LUAD and can serve as prognostic biomarkers. Further, Withanolides can inhibit the activity of LDHA and can be tested as an adjuvant treatment. Conclusion: We conclude that LDHA is overexpressed in LUAD, and the patients with high expression of LDHA exhibit poor prognosis. Further, the TMPO-AS1-hsa-let-7c-5p-LDHA ceRNA network can regulate aerobic glycolysis, thereby facilitating tumor growth in lung cancer.
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