Investigation of mRNA Levels of PFK-1, LDH-A, p53, and HIF-1α Genes Involved in Metabolic Reprogramming in Non-small Cell Lung Carcinoma
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...
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| Format: | Article |
| Language: | English |
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Kerman University of Medical Sciences
2023-01-01
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| Series: | Journal of Kerman University of Medical Sciences |
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| Online Access: | https://jkmu.kmu.ac.ir/article_92132.html |
| _version_ | 1797894869685895168 |
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| author | Fatemeh Shakeri Mehdi Ebrahimi Shohre Zare Karizi |
| author_facet | Fatemeh Shakeri Mehdi Ebrahimi Shohre Zare Karizi |
| author_sort | Fatemeh Shakeri |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T07:16:12Z |
| format | Article |
| id | doaj.art-6a986233cc5c4c1faeb89aea2f0c8953 |
| institution | Directory Open Access Journal |
| issn | 2008-2843 |
| language | English |
| last_indexed | 2024-04-10T07:16:12Z |
| publishDate | 2023-01-01 |
| publisher | Kerman University of Medical Sciences |
| record_format | Article |
| series | Journal of Kerman University of Medical Sciences |
| spelling | doaj.art-6a986233cc5c4c1faeb89aea2f0c89532023-02-25T05:44:54ZengKerman University of Medical SciencesJournal of Kerman University of Medical Sciences2008-28432023-01-01301172410.34172/JKMU.2023.03Investigation of mRNA Levels of PFK-1, LDH-A, p53, and HIF-1α Genes Involved in Metabolic Reprogramming in Non-small Cell Lung CarcinomaFatemeh Shakeri0Mehdi Ebrahimi1Shohre Zare Karizi 2 Department of Genetics, College of Biological Sciences, Varamin-Pishva Branch, Islamic Azad University, Varamin, Iran Department of Biochemistry and Biophysics, College of Biological Sciences, Varamin-Pishva Branch, Islamic Azad University, Varamin, Iran Department of Genetics, College of Biological Sciences, Varamin-Pishva Branch, Islamic Azad University, Varamin, IranBackground: 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.https://jkmu.kmu.ac.ir/article_92132.htmlkeywords keywords: lung cancer warburg effect phosphofructokinase-1 lactate dehydrogenase hypoxia-inducible factor-1 |
| spellingShingle | Fatemeh Shakeri Mehdi Ebrahimi Shohre Zare Karizi Investigation of mRNA Levels of PFK-1, LDH-A, p53, and HIF-1α Genes Involved in Metabolic Reprogramming in Non-small Cell Lung Carcinoma Journal of Kerman University of Medical Sciences keywords keywords: lung cancer warburg effect phosphofructokinase-1 lactate dehydrogenase hypoxia-inducible factor-1 |
| title | Investigation of mRNA Levels of PFK-1, LDH-A, p53, and HIF-1α Genes Involved in Metabolic Reprogramming in Non-small Cell Lung Carcinoma |
| title_full | Investigation of mRNA Levels of PFK-1, LDH-A, p53, and HIF-1α Genes Involved in Metabolic Reprogramming in Non-small Cell Lung Carcinoma |
| title_fullStr | Investigation of mRNA Levels of PFK-1, LDH-A, p53, and HIF-1α Genes Involved in Metabolic Reprogramming in Non-small Cell Lung Carcinoma |
| title_full_unstemmed | Investigation of mRNA Levels of PFK-1, LDH-A, p53, and HIF-1α Genes Involved in Metabolic Reprogramming in Non-small Cell Lung Carcinoma |
| title_short | Investigation of mRNA Levels of PFK-1, LDH-A, p53, and HIF-1α Genes Involved in Metabolic Reprogramming in Non-small Cell Lung Carcinoma |
| title_sort | investigation of mrna levels of pfk 1 ldh a p53 and hif 1α genes involved in metabolic reprogramming in non small cell lung carcinoma |
| topic | keywords keywords: lung cancer warburg effect phosphofructokinase-1 lactate dehydrogenase hypoxia-inducible factor-1 |
| url | https://jkmu.kmu.ac.ir/article_92132.html |
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