MBD2 inhibits the malignant characteristic of lung adenocarcinoma through the epigenetic modulation of TET1 and mir-200s.

MBD2 inhibits the malignant characteristic of lung adenocarcinoma through the epigenetic modulation of TET1 and mir-200s. Am J Pathol. 2019 Feb 05;: Authors: Pei YF, Xu XN, Wang ZF, Wang FW, Wu WD, Geng JF, Liu XQ Abstract It has been reported that disorders of epigenetic modulation play a critical role in carcinogenesis. MBD2 is known to act as an epigenetic modulator in various types of tumors; however, the role of MBD2 in lung adenocarcinoma (LUAD) remains unclear. Here, we demonstrated the down-regulation of MBD2 in LUAD compared with adjacent nontumor tissues. The down-regulation of MBD2 in LUAD was correlated with metastasis and poor survival. Additionally, MBD2 inhibited tumor metastasis by maintaining the expression of the mir-200s, which suppressed the invasive properties of tumors. Also, MBD2 positively correlated with 5-hmC content in mir-200s promoter. The conventional view is that MBD2 acts as a transcriptional suppressor. However, the data revealed that MBD2 may act as transcriptional activator by recruiting TET1 and forming a chromatin-remodeling complex. The MBD2-TET1 complex locates to the TET1 promoter and removes the methyl residues in this region, thereby activating TET1 transcription. TET1 also acted as tumor suppressor in LUAD. Taken together, the data demonstrate the correlation between MBD2, mir-200s, and TET1, and tumor suppressive effect of MBD2 through up-regulation of TET1 and the mir-200s. PMID: 3...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research