Long Non-Coding RNA LINC00525 Promotes the Stemness and Chemoresistance of Colorectal Cancer by Targeting miR-507/ELK3 Axis
INTERNATIONAL JOURNAL OF STEM CELLS
Authors: Wang, Shunsheng; Li, Jing; Yang, Xiaopeng
Abstract
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 sternness 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. Overcxpression 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 s prognostic marker of CRC. Conclusions: LINC00525 enhanced sternness properties and increased sensitivities of CRC cells to oxaliplatin by targeting miR-507/ELK3 axis.
High ELK3 expression is associated with the VEGF-C/VEGFR-3 axis and gastric tumorigenesis and enhances infiltration of M2 macrophages
FUTURE MEDICINAL CHEMISTRY
Authors: Wang, Dazhi; Jiao, Zheng; Ren, Chunling
Abstract
Aim: To assess the expression and effect of ELK3 in gastric cancer, along with its associations with the VEGF-C/VEGFR-3 axis, IC50 of the VEGFR-3 inhibitor axitinib and immune infiltration of M2-polarized macrophages in gastric cancer, and to analyze the possible epigenetic regulation mechanism. Materials & methods: Expression profiles and methylation data from 1645 samples were obtained and examined from multi-institutional public datasets. The associations were assessed by multiple analysis methods. Results: Elevated ELK3 is associated with the VEGF-C/VEGFR-3 axis and tumorigenesis, reduces the effect of axitinib in vitro, enhances immune infiltration of M2 macrophages and affects clinical outcomes. Hypomethylation contributes to the upregulation of ELK3 in gastric cancer. Conclusions: ELK3 is a potential therapeutic target which reduces the effect of axitinib and enhances infiltration of M2-polarized macrophages.
COA
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