Identification of DBCCR1 as a suppressor in the development of lung cancer that is associated with increased DNA methyltransferase 1

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.

Hsa_circ_0040809 regulates colorectal cancer development by upregulating methyltransferase DNMT1 via targeting miR‐515‐5p

“…29 For example, DNMT1 promotes tumorigenesis and development of lung cancer by promoting supermethylation of the CpG islands of the cancer suppressor DBCCR1. 30 DNMT1 inhibits PTEN expression in bladder cancer by maintaining the state of CpG methylation in the promoter. 31 It has been reported that DNMT inhibitors can reverse the supermethylation of tumor suppressors and activate their expression, thereby inhibiting the malignant progression of tumors.…”

EZH2-mediated epigenetic silencing of ZIC4 in hepatocellular carcinoma

“…Many studies have con rmed the effect of CpG island hypermethylation on the regulation of cancerassociated genes in tumorigenesis and progression [17]. For example, the methylation degree of miR-608 was higher in two cancer cells lines compared with normal cell line with the methylation level of 91.4% and 87.3% respectively, and also proposed that CpG islands hypermethylation might cause the silencing of mRNA expression [18].…”

Epigenetic inactivation of HOXD10 is associated with human colon cancer via inhibiting the RHOC/AKT/MAPK signaling pathway

“…Existing research indicated that the methylation of cancer suppressor genes was in close relationship with cancer development [26]. Growing evidence showed clearly that the CpG island hypermethylation in oncogenes played a fundamental role in the process of colon cancer development [27, 28]. Previous studies have showed that HOXD10 which was aberrantly hypermethylated in papillary thyroid cancer may act as a tumor suppressor [29].…”