Abstract
BackgroundRas association domain family 1A gene (RASSFlA) is a candidate suppressor gene, Lack of RASSF1A expression was found in lung cancer. High DNA methylation at the promoter region is the main reason for inactivating RASSF1A transcription.MethodsIn this study, we examined RASSF1A’s methylation status and its mRNA expression level between non-small cell lung cancer cell line A549 and anti-Cisplatin cell strain A549DDP, Furthermore, methylation of A549DDP was reversed by treatment of 5-Aza-2′ - deoxycytidine (5-Aza-cdR),a DNA methyltransferase inhibitor.ResultsWe found that RASSF1A’s methylation status and its mRNA expression were obvious differences between A549 and A549DDP. 5-Aza-CdR treatment remarkablly reduced cell vability of A549DDP. Moreover, 5-Aza-CdR treatment induced A549DDP cell apoptosis in a dose dependent manner with declining cell percentage in S and G2/M stage, and increasing proportion in G0/G1 stage. Cell motility was blocked in G0/G1 stage. All of A549DDP cells showed unmethylated expression, its high methylation status was reversed in a dose-dependent manner within a certain range.ConclusionsThe abnormal gene methylation status of RASSF1A is a molecular biomarker in lung cancer diagnosis, treatment and prognosis.
Highlights
Lung cancer is one of the most common malignant tumors with highest incidence and morbidity [1,2]
We studied the abnormal gene methylation status of RASSF1A in non-small cell lung cancer (NSCLC) cell line A549 and anti-Cisplatin cell strain A549DDP and suggested that methyaltion of RASSF1A is a molecular biomarker in cancer diagnosis, treatment and prognosis
RASSF1A methylation in lung cancer cells To investigate the different status of RASSF1A DNA methylation in lung cancer cells, we examined DNA methylation of RASSF1A in the Cisplatin-resistant cell strain A549DDP and A549 lung cancer cells by Methylation-specific PCR (MSP)
Summary
Lung cancer is one of the most common malignant tumors with highest incidence and morbidity [1,2]. Late detection is a major contributor to these high mortality rates [3]. Most patients are already at the late stage of lung cancer when they are diagnosed. Cisplatin [4] is the first-line chemotherapy drug, used in the late stage of lung cancer. Cisplatin and other drugs are not efficient chemotherapy in non-small cell lung cancer (NSCLC). It is the most urgent to conquer the drug-resistance of NSCLC in cancer therapy. Ras association domain family 1A gene (RASSFlA) is a candidate suppressor gene, Lack of RASSF1A expression was found in lung cancer. High DNA methylation at the promoter region is the main reason for inactivating RASSF1A transcription
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