Long Non-Coding RNA LINC00525 Promotes the Stemness and Chemoresistance of Colorectal Cancer by Targeting miR-507/ELK3 Axis

BACKGROUND AND OBJECTIVES: This study aims to explore the effects of a long non-coding RNA, LINC00525, on colorectal cancer (CRC) and its underlying molecular mechanisms. METHODS: The qPCR, MTT, colony formation, Western blotting, Luciferase reporter and biotin pull-down, shRNA knockdown and DNA fragmentation assays were performed in this study. RESULTS: High expressions of LINC00525 were associated with poor prognosis of CRC patients. LINC00525 knockdown decreased stemness properties and increased sensitivities to oxaliplatin. MiR-507 was a direct target of LINC00525 and overexpression of miR-507 significantly decreased abilities of tumorsphere formation and cell growth. Overexpression of miR-507 resulted in a decrease of expression of cancer stem cell markers and the increase of apoptosis rates. MiR-507 regulated the expression of ELK3. In addition, LINC00525 knockdown decreased the expression of ELK3. Restoration of ELK3 expression abrogated the effects of LINC00525 knockdown. LINC00525 could be served as prognostic marker of CRC. CONCLUSIONS: LINC00525 enhanced stemness properties and increased sensitivities of CRC cells to oxaliplatin by targeting miR-507/ELK3 axis.

ELK-3 interference inhibits the epithelial-mesenchymal transition of human hepatocellular carcinoma cells / 基础医学与临床

Objective To investigate the relationship of ELK-3 and epithelial-mesenchymal transition ( EMT) for ex-ploring its possible mechanism .Methods The human hepatocellular carcinoma cells ( HCC) were divided into small interference RNA transfection group and Ras-ELK-3 pathway inhibitor group .The protein level of ELK-3 target gene EGR-1 E-cadherin ,vimentin and p38 in HCC were determined by Western blot analysis .Results The protein level of ELK-3 and its target gene EGR-1 in treated human hepatocellular carcinoma cells significantly decreased as compared with the negative control group (P<0.01).The protein level of E-cadherin was significantly increased (P<0.01), while vimentin and p38 were decreased in HCC cells with ELK-3 interference (P<0.01).Conclusions ELK-3 in-terference can inhibit the epithelial-mesenchymal transition of HCC cells by down-regulating p38.

Elk-3 Contributes to the Progression of Liver Fibrosis by Regulating the Epithelial-Mesenchymal Transition

BACKGROUND/AIMS: The role of Elk-3 in the epithelial-mesenchymal transition (EMT) during liver fibrogenesis remains unclear. Here, we determined the expression of Elk-3 in in vitro and in vivo models and in human liver fibrotic tissues. We also investigated the molecular relationships among Elk-3, early growth response-1 (Egr-1), and the mitogen activated protein kinases (MAPK) pathway during EMT in hepatocytes. METHODS: We established anin vitro EMT model in which normal mouse hepatocyte cell lines were treated with transforming growth factor (TGF)-β1 and a CCl4-induced liver fibrosis model. Characteristics of EMT were determined by evaluating the expression levels of related markers. The expression of Elk-3 and its target Egr-1 were analyzed using Western blotting. Gene silencing of Elk-3 was performed using an siRNA knockdown system. RESULTS: The expression levels of mesenchymal markers were increased during TGF-β1-induced EMT of hepatocytes. The expression levels of Elk-3 and Egr-1 were significantly (p<0.05) increased during the EMT of hepatocytes, in CCl₄-induced mouse liver fibrotic tissues, and in human liver cirrhotic tissues. Silencing of Elk-3 and inhibition of the Ras-Elk-3 pathway with an inhibitor suppressed the expression of EMT-related markers. Moreover, Elk-3 expression was regulated by p38 MAPK phosphorylation during EMT. CONCLUSIONS: Elk-3 contributes to the progression of liver fibrosis by modulating the EMT via the regulation of Egr-1 under MAPK signaling.