LINC00152 upregulates ZEB1 expression and enhances epithelial-mesenchymal transition and oxaliplatin resistance in esophageal cancer by interacting with EZH2

Abstract

Background Expression of the long non-coding mRNA LINC00152 has been reported to correlate with cancer cell resistance to oxaliplatin (L-OHP). However, little is known regarding the molecular mechanism of LINC00152 in esophageal cancer (EC). Hence, we intended to characterize the role of LINC00152 in EC, with a special focus on epithelial-mesenchymal transition (EMT) and L-OHP resistance. Methods We collected EC tissues and identified EC cell lines with higher L-OHP resistance, and then characterized expression patterns of LINC00152, Zeste Homologue 2 (EZH2), Zinc finger e-box binding homeobox (ZEB1) and EMT-related genes using RT-qPCR and Western blot analysis. Furthermore, their functional significance was identified by gain and loss-of-function experiments. The relationship among LINC00152, EZH2 and ZEB1 was examined using RIP, RNA pull-down and ChIP assays. Additionally, resistance of EC cells to L-OHP was reflected by CCK-8 assay to detect cell viability. Animal experiments were also conducted to detect the effects of the LINC00152/EZH2/ZEB1 on EMT and L-OHP resistance. Results LINC00152, EZH2 and ZEB1 were highly expressed in EC tissues and Kyse−150/TE-1 cells. As revealed by assays in vitro and in vivo, LINC00152 positively regulated ZEB1 expression through interaction with EZH2 to enhance EMT and L-OHP resistance in EC cells. In contrast, silencing of LINC00152 contributed to attenuated EMT and drug resistance of EC cells to L-OHP. Conclusions Our study demonstrates that LINC00152/EZH2/ZEB1 axis can regulate EMT and resistance of EC cells to L-OHP, thus presenting a potential therapeutic target for EC treatment.

H3.3K27M Mutation Promotes The Migration and Invasion of Glioma Cells By Activating β-Catenin/USP1 Signaling

“…Chen et al identi ed a novel metastasis-promoting lncRNA, MRPL23-AS1, which mediates the transcriptional silencing of E-cadherin by forming an RNA-protein complex with EZH2 [21]. EZH2 is also closely associated with the EMT of other tumors, such as pancreatic cancer, head and neck squamous cell carcinoma and esophageal cancer [22][23][24]. It has been reported that the EZH2 inhibitors MC4040 and MC404 reverse EMT and hamper cell migration and invasion, attenuating the glioma malignant phenotype [25].…”

Long Non-Coding RNA LINC00152 Regulates Self-Renewal of Leukemia Stem Cells and Induces Chemo-Resistance in Acute Myeloid Leukemia

“…Furthermore, posttranslational modifications of PARP1, such as mono (ADP-ribosyl)-ation ( 36 , 37 ), phosphorylation, methylation, and acetylation, can modulate its activity. Thus, LINC00152 may influence PARP1 posttranslational modification by binding to the enhancer of zeste homologue 2 (EZH2) ( 38 ) or participate in the phosphatidylinositol 3-kinase/AKT signaling pathway ( 39 ), which may also be important for PARP1 expression and activity.…”

The Hypoxia–Long Noncoding RNA Interaction in Solid Cancers

“…In multiple cancers, LINC00152 supports EMT and metastasis by positively regulating the level of ZEB1, PI3K, and AKT [ 166 , 167 ]. In gallbladder cancer, LINC00152 was also observed to exhibit EMT- and metastasis-promoting activities via sponging miR-138-5p that targets HIF-1α [ 146 ] ( Figure 2 and Table 2 ).…”