Investigation of mRNA Levels of PFK-1, LDH-A, p53, and HIF-1α Genes Involved in Metabolic Reprogramming in Non-small Cell Lung Carcinoma

Abstract

Background: It is expected that the expression of key enzymes of the glycolysis pathway, specially PFK-1, increases tumor cells and so enhances the function of this pathway. The p53 and HIF-1 proteins are regulators of the expression of PFK-1 and LDH enzymes. This study was performed to investigate changes in the expression of PFK-1, LDH-A, p53, and HIF-1α genes to identify metabolic changes in non-small cell lung carcinoma (NSCLC) samples. Methods: A number of 30 tumors and their adjacent normal tissue samples from surgically approved NSCLC patients were used. Total RNA from each tissue was extracted. The changes in mRNA levels of PFK-1M, LDHA, p53, and hypoxia-inducible factor-1 (HIF-1α) genes were evaluated in tumor and normal tissues of all patients using the real-time polymerase chain reaction (PCR) method. Finally, statistical analysis was used to determine significant differences and the relationship between changes in mRNA levels. Results: According to the results, there was no significant difference in the mRNA levels of these genes between tumor and normal tissues. A significant difference in the mRNA level of lactate dehydrogenase A (LDHA) between adenocarcinoma (AdC) and squamous cell carcinoma (SqCC) tumor types was observed (P=0.014). Also, the difference between the mRNA level of LDHA and HIF-1α in metastatic and non-metastatic samples was significant (P=0.035 and P=0.046 respectively). Age and male gender were directly associated with an increased risk of NSCLC. Conclusion: The results of the present study revealed that the increase in mRNA level of PFK-1 and p53 may be involved in NSCLC initiation, and an increase in LDH-A and HIF-1a is associated with a metastatic phenotype.

Keywords

• keywords keywords: lung cancer warburg effect phosphofructokinase-1 lactate dehydrogenase hypoxia-inducible factor-1