长链非编码RNA LINC00525通过靶向miR-507/ELK3轴促进结直肠癌的干性和化疗耐药性。

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

作者信息

Wang Shunsheng, Li Jing, Yang Xiaopeng

机构信息

Department of Colorectal Surgery, Yidu Central Hospital of Weifang City, Qingzhou, China.

出版信息

Int J Stem Cells. 2019 Jul 31;12(2):347-359. doi: 10.15283/ijsc19041.

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.

背景与目的

本研究旨在探讨长链非编码RNA LINC00525对结直肠癌（CRC）的影响及其潜在分子机制。

方法

本研究进行了qPCR、MTT、集落形成、蛋白质免疫印迹、荧光素酶报告基因和生物素下拉、shRNA敲低及DNA片段化分析。

结果

LINC00525高表达与CRC患者预后不良相关。LINC00525敲低降低了干性特征并增加了对奥沙利铂的敏感性。MiR-507是LINC00525的直接靶点，miR-507过表达显著降低了肿瘤球形成能力和细胞生长能力。miR-507过表达导致癌症干细胞标志物表达降低，凋亡率增加。miR-507调节ELK3的表达。此外，LINC00525敲低降低了ELK3的表达。恢复ELK3表达可消除LINC00525敲低的影响。LINC00525可作为CRC的预后标志物。