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Bioinformatics analysis and expression study of fumarate hydratase in lung cancer
Zongjuan Ming1, Meihua Jiang1, Wei Li1
1Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, 710004, China.
Background:
As its etiology and pathogenesis is obscure, illustrating the molecular mechanism of lung cancer has become a serious and urgent task. Studies have shown that fumarate hydratase (FH) is a tumor suppressor related to tumorigenesis, development, and invasion. Our aim was to analyze the biological information of FH, and detect the messenger ribonucleic acid (mRNA) and protein expression of FH in lung cancer cells to explore its role in tumorigenesis and in the development of lung cancer.
Method:
We analyzed the biological characteristics of FH, then utilized reverse transcription-polymerase chain reaction (RT-PCR) to study FH mRNA expression in A549 and 16 human bronchial epithelial (HBE) cell lines. The protein expression of FH was detected in 57 cases of human lung cancer tissues and 19 cases of normal lung tissues by immunohistochemistry.
Results:
1. Bioinformatic analysis: FH mainly exist in the mitochondria; the common structural elements of FH are mainly α-helix, random coil, β-turn, and extended strand; there are five possible transmembrane domains in the entire polypeptide chain; FH is a hydrophilic and soluble protein. 2. RT-PCR result: FH mRNA expression was downregulated in A549 cells compared with 16HBE cells. 3. Immunohistochemistry: FH protein expression was significantly lower in lung cancer cells than in normal lung tissues (P < 0.05), but was not correlated with the patients' age, gender, tumor size, pathological type, or lymph node, distant, or tumor node metastasis stage.
Conclusion:
FH was under-expressed in lung cancer, suggesting that it may be an indicator of tumorigenesis and could be a potential target for therapies against lung cancer in the future.
Insights
Fumarate hydratase (FH) is downregulated in lung cancer cells, indicating its potential role in tumorigenesis. This suggests FH could be a therapeutic target for lung cancer treatment.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Lung cancer pathogenesis remains unclear, necessitating research into its molecular mechanisms.
- Fumarate hydratase (FH) is implicated as a tumor suppressor involved in cancer development and invasion.
Purpose of the Study:
- To investigate the biological characteristics of FH.
- To analyze FH mRNA and protein expression in lung cancer cells.
- To explore the role of FH in lung cancer initiation and progression.
Main Methods:
- Bioinformatic analysis of FH.
- Reverse transcription-polymerase chain reaction (RT-PCR) to assess FH mRNA levels in A549 and 16HBE cells.
- Immunohistochemistry to evaluate FH protein expression in lung cancer and normal lung tissues.
Main Results:
- Bioinformatic analysis revealed FH is a mitochondrial, hydrophilic protein with specific structural elements and transmembrane domains.
- RT-PCR showed decreased FH mRNA expression in A549 lung cancer cells compared to 16HBE cells.
- Immunohistochemistry demonstrated significantly lower FH protein expression in lung cancer tissues versus normal tissues, independent of clinical parameters.
Conclusions:
- FH is underexpressed in lung cancer, suggesting it acts as a tumor suppressor.
- FH may serve as a biomarker for lung cancer tumorigenesis.
- FH represents a potential therapeutic target for future lung cancer treatments.
