Hypermethylation of the PTTG1IP promoter leads to low expression in early-stage non-small cell lung cancer.

Despite the clinical requirement for early diagnosis, the early events in lung cancer and their mechanisms are not fully understood. Pituitary tumor transforming gene 1 binding factor () is a tumor-associated gene; however, to the best of our knowledge, its association with lung cancer has not been reported. The present study analyzed expression in early-stage non-small cell lung cancer (NSCLC) samples and investigated its epigenetic regulatory mechanisms. The results revealed that the mRNA level of in NSCLC tissues was significantly downregulated by 43% compared with that in adjacent tissues. In addition, overexpression of this gene significantly inhibited cell proliferation. According to data from The Cancer Genome Atlas, a significant negative correlation was identified between the gene methylation level and expression level in lung adenocarcinoma and lung squamous cell carcinoma cases. Reduced representation bisulfite sequencing (RRBS) analysis of six paired early-stage NSCLC tissue samples indicated that the CpG island shore of the promoter is hypermethylated in lung cancer tissues, which was further validated in 12 paired early-stage NSCLC samples via bisulfite amplicon sequencing. Following treatment with 5-aza-2'-deoxycytidine to reduce DNA methylation in the promoter region, the mRNA level increased, indicating that the promoter DNA methylation level negatively regulates transcription. In conclusion, in early-stage NSCLC, the gene is regulated by DNA methylation in its promoter region, which may participate in the development and progression of lung cancer.