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// Guoren Zhou 1, * , Jinjun Ye 2, * , Ying Fang 1 , Zhi Zhang 3 , Jingyuan Zhang 4 , Lei Sun 5 and Jifeng Feng 1 1 Department of Chemotherapy, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210000, Jiangsu, China 2 Department of Radiotherapy, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210000, Jiangsu, China 3 Department of Thoracic Surgery, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210000, Jiangsu, China 4 Department of Pathology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210000, Jiangsu, China 5 Department of Medical Iconography, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210000, Jiangsu, China * These authors have contributed equally to this work Correspondence to: Jifeng Feng, email: jsfjf2016@163.com Keywords: lung cancer, DNA methyltransferase, tumor suppressor, DBCCR1, epigenetics Received: January 04, 2017 Accepted: February 08, 2017 Published: March 02, 2017 ABSTRACT Accumulating evidence has pointed to a role of the CpG island hypermethylation in the regulation of cancer-related genes in tumor progression. However, the biological impacts in cancer pathogenesis associated with down-regulation of such gene targets remains elusive. Here we focused on a potential target of hypermethylation, DBCCR1 (deleted in bladder cancer chromosome region 1), a gene encoding a candidate tumor suppressor. We found that the expression of DBCCR1 is significantly lower in the lung cancer tissues compared with adjacent non-tumor tissues of patients. Importantly, the decreased DBCCR1 was found correlated with more advanced stages of cancer, and with a significantly shorter survival of patients. Genetic silencing DBCCR1 in human lung cancer cell line A549 resulted in an enhanced proliferation, migration, and invasion capacity. Conversely, restoring DBCCR1 expression blocked the growth and inhibited the ability of cancer cell in migration and invasion. Interestingly, DBCCR1 attenuates the expression of DNMT1 (DNA methyltransferase 1), suggesting a reciprocal regulation between genetic silencing of cancer suppressor genes and activating DNA methylation. Our data thus implicates DBCCR1 downregulation as a potential module in the pathogenesis of lung cancer through DNA methylation. |
