Fig. 3

The mutual roles of DNA methylation and lncRNAs for tumor progression in gastric cancer. As shown on the right, abnormal DNA methylation regulates the expression of lncRNAs as tumor suppressor genes in gastric cancer. LncRNA Uc.160+ and lncRNA linc00086 are hypermethylated in GC cells via, respectively, evoking Src/MEK/ERK and p38 pathway and regulating MeCP2 by ERK1/2 signaling pathways. Uc.160+ could contribute to the repression of PTEN expression, and MAPK signaling pathway could bring about the inactivation of RUNX3 via evoking Src/MEK/ERK and p38 pathway. SPRY4-IT1 is hypermethylated in GC cells resulting in tumor progression due to the EMT attributed to decrease of E-cadherin and increase of Vimentin. C5orf66-AS1 is hypermethylated in GCA tissues and cell lines, which is associated with its lower expression possibly through abrogating Sp1 binding. LncRNA MEG3, lncRNA AFDN-DT, and LOC100130476 are hypermethylated in GC. Their endings are shown in the figure. On the other side, lncRNAs regulate the abnormal DNA methylation of tumor-related genes in gastric cancer. The PLZF is hypermethylated through regulation of LncRNA ANRIL remarkably in GC tissues and cell lines, and the progression derives from EMT that is negatively correlated with E-cadherin but positively with Vimentin and N-cadherin. MED18 is hypermethylated through regulation of lncRNA SNHG3 by binding to EZH2. PCDH10 is hypermethylated by lncRNA HOTAIR through interacting with miR-148 and DNMT1 in GC. ACOT7 was hypermethylated by lncRNA NMRAL2P through binding to DNMT3b in GC cells. LncRNA LUCAT1 induces hypermethylation of CXXC4 which can regulate Wnt/β-catenin signaling closely related to the development and progression of GC. LncRNA HOTTIP enabled HoxA13 to be hypermethylated and it can be the target of HoxA13 reversely. And IGFBP-3 could interact with HoxA13 as its downstream target in GC and can be modulated by p53 pathway. LncRNA AK058003 is upregulated by hypoxia and regulate the hypomethylation of SNCG. Similar to AK058003, lncRNA AK123702 is also upregulated by hypoxia and capable of regulating the hypomethylation of EGFR in GC cells. Their endings are shown in the figure