ABSTRACT
Lung cancer is one of the primary causes of cancer-induced death among the world. Although the network of molecular implicated in lung cancer is gradually revealed, the exact molecular mechanism of its occurrence and development has not been fully elucidated. As a class of small and endogenous single-stranded non-coding RNAs, microRNAs (miRNAs) are found in a wide range of organisms from plants, viruses to humans. miRNAs involve various functions in normal lung tissue development. They take part in a large amount of biological processes including cell growth, metabolism, proliferation and differentiation. However, aberrant expression of miRNAs could induce the occurrence, development, invasion and metastasis of lung tumor, so it is deemed the novel biomarkers. Similar to that of protein-coding genes, expression and function of miRNA are regulated by various factors and the epigenetic network which includes DNA methylation and histone modification. Moreover, key enzymes driving epigenetic modifications are regulated by miRNAs. Therefore, better understanding of inextricable linkage between miRNAs and epigenome will provides a basis for the feasibility of miRNA-orientated diagnostic, therapeutic and prognostic strategies related to lung cancer in future.
ABSTRACT
<p><b>BACKGROUND</b>Recently, the p14 ARF gene has emerged as a new putative tumor suppressor gene, and the alteration of p14 ARF gene is closely related to development of multiple human tumors. The aberrant promoter methylation as a mechanism of inactivation of p14 ARF gene might participate in tumorigenesis. The aim of this study is to investigate promoter methylation status and protein expression of p14 ARF gene in pulmonary squamous cell carcinoma and adenocarcinoma, and to value the role of p14 ARF promoter methylation in carcinogenesis of non-small cell lung cancer.</p><p><b>METHODS</b>Promoter methylation status and protein expression of p14 ARF gene were analyzed in 40 cases of pulmonary squamous cell carcinoma and adenocarcinoma by methylation specific polymerase chain reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR) and immunohistochemistry (IHC).</p><p><b>RESULTS</b>The positive rate of p14 ARF promoter methylation in tumor tissues and normal tissues adjacent to cancer was 17.5% (7/40) and 2.5% (1/40) respectively (P= 0.025 ). The results of RE-PCR were consistent with the above. The positive rate of p14 ARF protein in tumor tissues was significantly lower than that in normal tissues adjacent to cancer (P=0.003). Promoter methylation and protein expression of p14 ARF gene showed a significantly negative correlation (r=-0.56, P= 0.001 ), and both of them did not correlate statistically with the clinicopathologic characteristics of patients such as histological classification, TNM stages, differentiation grade and lymph node involvement.</p><p><b>CONCLUSIONS</b>Promoter methylation is a crucial mechanism of inactivation of p14 ARF gene. Promoter methylation of p14 ARF gene might be involved in carcinogenesis of non-small cell lung cancer, and it is an early event in development process of non-small cell lung cancer.</p>