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MicroRNAs (miRNAs), a class of small noncoding RNAs, play important roles in tumorigenesis by targeting mRNAs [13].DNMT3A and -B are directly regulated by the miRNA (miR)-29 family (29a, 29b, and 29c) [14]. The expression of MiR-29 family members is down-regulated in lung cancer[15], which has been associated with promoter methylation and transcription factor regulation [16,17]. However, the association between DNMT upregulation and over-methylation of the WIF-1 gene and whether restoration of miR-29s suppresses Wnt signaling by modulating the methylation of WIF-1 remains unclear. In addition, the potential self-regulation of the expression of miR-29 family members through DNMT3A and -B needs clarification. In the present study, we investigated the roles of three DNMTs in the expression of WIF-1 and linked miR-29s to the Wnt/b-catenin signaling pathway, investigating their effects on cell growth and apoptosis. We showed that the expression of miR-29a and miR-29b is regulated by DNMT3A and DNMT3B, suggesting the existence of a positive feedback loop. Our findings shed light on the role of aberrant Wnt signaling in NSCLC. |
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