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Open Access 01-12-2018 | Research

The role of HGF-MET pathway and CCDC66 cirRNA expression in EGFR resistance and epithelial-to-mesenchymal transition of lung adenocarcinoma cells

Authors: Nithila A. Joseph, Shiow-Her Chiou, Zoe Lung, Cheng-Lin Yang, Tze-Yi Lin, Hui-Wen Chang, H. Sunny Sun, Sachin Kumar Gupta, Laising Yen, Shulhn-Der Wang, Kuan-Chih Chow

Published in: Journal of Hematology & Oncology | Issue 1/2018

Abstract

Background

Epithelial-to-mesenchymal transition (EMT) has, in recent years, emerged as an important tumor cell behavior associated with high metastatic potential and drug resistance. Interestingly, protein SUMOylation and hepatocyte growth factor could respectively reduce the effect of small molecule inhibitors on tyrosine kinase activity of mutated epidermal growth factor receptor of lung adenocarcinomas (LADC). The actual mechanism is yet to be resolved.

Methods

Immunohistochemistry was used to stain proteins in LADC specimens. Protein expression was confirmed by Western blotting. In vitro, expression of proteins was determined by Western blotting and immunocytochemistry. Levels of circular RNA were determined by reverse transcription-polymerase chain reaction.

Results

SAE2 and cirRNA CCDC66 were highly expressed in LADC. Expression of SAE2 was mainly regulated by EGFR; however, expression of cirRNA CCDC66 was positively regulated by FAK and c-Met but negatively modulated by nAchR7α. EGFR-resistant H1975 also highly expressed cirRNA CCDC66. Immediate response of hypoxia increased phosphorylated c-Met, SAE2, and epithelial-to-mesenchymal transition. Either activation of FAK or silencing of nAchR7α increased cirRNA CCDC66.

Conclusions

HGF/c-Met regulates expression of SAE2 and cirRNA CCDC66 to increase EMT and drug resistance of LADC cells. Multimodality drugs concurrently aiming at these targets would probably provide more benefits for cancer patients.

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Title: The role of HGF-MET pathway and CCDC66 cirRNA expression in EGFR resistance and epithelial-to-mesenchymal transition of lung adenocarcinoma cells
Authors: Nithila A. Joseph
Shiow-Her Chiou
Zoe Lung
Cheng-Lin Yang
Tze-Yi Lin
Hui-Wen Chang
H. Sunny Sun
Sachin Kumar Gupta
Laising Yen
Shulhn-Der Wang
Kuan-Chih Chow
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Journal of Hematology & Oncology / Issue 1/2018
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-018-0557-9

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Abstract

Background

Methods

Results

Conclusions

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