Oncotarget

Research Papers:

Long noncoding RNA ROR regulates chemoresistance in docetaxel-resistant lung adenocarcinoma cells via epithelial mesenchymal transition pathway

Yan Pan, Jing Chen, Leilei Tao, Kai Zhang, Rui Wang, Xiaoyuan Chu and Longbang Chen _

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Oncotarget. 2017; 8:33144-33158. https://doi.org/10.18632/oncotarget.16562

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Abstract

Yan Pan1,*, Jing Chen1,*, Leilei Tao1,*, Kai Zhang1,*, Rui Wang1, Xiaoyuan Chu1, Longbang Chen1

1Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China

*The authors contributed equally to this work

Correspondence to:

Longbang Chen, email: chenlongbang@yeah.net

Keywords: lung adenocarcinoma (LAD), linc-ROR, miR-145, FSCN1, chemoresistance

Received: January 16, 2017     Accepted: March 16, 2017     Published: March 25, 2017

ABSTRACT

Emerging evidence indicates that the dysregulation of long non-coding RNAs (lncRNAs) contributes to the development and progression of lung adenocarcinoma (LAD), however the underlying mechanism of action of lncRNAs remains unclear. It is well known that the effective treatment of cancers has been hindered by drug resistance in the clinical setting. Epithelial-mesenchymal transition (EMT) has been recognized to be involved in acquiring drug resistance, cell migration and invasion properties in several types of cancer. Docetaxel-resistant LAD cells established previously in our lab present chemoresistant and mesenchymal features. Long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR), was first discovered in induced pluripotent stem cells (iPSCs) and was upregulated in docetaxel-resistant LAD cells. In this study, we tried to make clarification of lincRNA-related mechanisms underlying EMT followed by acquired resistance to chemotherapy in LAD. In order to hit the mark, we made use of multiple methods including microarray analysis, qRT-PCR, western blotting analysis, loss/gain-of-function analysis, luciferase assays, drug sensitivity assays, wound-healing assay and invasion assay. We found that decreased expression of linc-ROR effectively reversed EMT in docetaxel-resistant LAD cells and sensitized them to chemotherapy. The function of linc-ROR exerted in LAD cells depended on the sponging of miR-145, therefore, releasing the miR-145 target FSCN1, and thus contributing to the acquisition of chemoresistance and EMT phenotypes of docetaxel-resistant LAD cells. Our findings revealed that linc-ROR might act as potential therapeutic target to overcome chemotherapy resistance in LAD.


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