Silencing of long non-coding RNA LINC01270 inhibits esophageal cancer progression and enhances chemosensitivity to 5-fluorouracil by mediating GSTP1methylation.

Esophageal cancer (EC) is a serious digestive malignancy which remains the sixth leading cause of cancer-related deaths worldwide. Emerging evidence suggests the involvement of long non-coding RNAs (lncRNAs) in the tumorigenesis of EC and thus, in this study we explored the potential effects of lncRNA LINC01270 on EC cell proliferation, migration, invasion and, drug resistance via regulation of glutathione S-transferase P1 (GSTP1) methylation. First, we screened out the EC-related differentially expressed lncRNAs, and the expression of our top candidate LINC01270 was quantified in EC tissues and cells. To define the role of LINC01270 in EC progression, we evaluated the proliferation, migration and invasion of EC cells when the LINC01270 was overexpressed or knocked down, in the presence of the GSTP1 methylation inhibitor SGI-1027 and 5-fluorouracil (5-FU). In addition, interaction between LINC01270 and methylation of the GSTP1 promoter was identified. Finally, we assessed transplantable tumor growth in nude mice. LINC01270 was up-regulated and GSTP1 was down-regulated in EC tissues and cells. Silencing of LINC01270 inhibited migration and invasion, and enhanced the sensitivity of 5-FU in EC cells. We found that LINC01270 recruited the DNA methyltransferases DNMT1, DNMT3A and DNMT3B initiating GSTP1 promoter methylation, thereby leading to the proliferation, migration, invasion and drug resistance of EC cells. Moreover, GSTP1 overexpression was observed to reverse the effects of LINC01270 overexpression on EC cells and their response to 5-FU. Taken together, this study shows that inhibition of LINC01270 can lead to suppression of EC progression via demethylation of GSTP1, highlighting this lncRNA as a potential target for EC treatment.