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miR-217 and CAGE form feedback loop and regulates the response to anti-cancer drugs through EGFR and HER2

Title
miR-217 and CAGE form feedback loop and regulates the response to anti-cancer drugs through EGFR and HER2
Authors
Kim, YoungmiKim, HyunaPark, DeokbumHan, MinhoLee, HansooLee, Yun SilChoe, JongseonKim, Young MyeongJeoung, Dooil
Ewha Authors
이윤실
SCOPUS Author ID
이윤실scopus
Issue Date
2016
Journal Title
ONCOTARGET
ISSN
1949-2553JCR Link
Citation
vol. 7, no. 9, pp. 10297 - 10321
Keywords
anti-cancer drug-resistanceCAGEEGFRHER2miR-217
Publisher
IMPACT JOURNALS LLC
Indexed
SCIE; SCOPUS WOS scopus
Abstract
MicroRNA array analysis revealed that miR-217 expression was decreased in anti-cancer drug-resistant Malme3M(R) cancer cells. CAGE, a cancer/testis antigen, was predicted as a target of miR-217. Luciferase activity and ChIP assays revealed a negative feedback relationship between CAGE and miR-217. miR-217 and CAGE oppositely regulated the response to anti-cancer drugs such as taxol, gefitinib and trastuzumab, an inhibitor of HER2. miR-217 negatively regulated the tumorigenic, metastatic, angiogenic, migration and invasion potential of cancer cells. The xenograft of Malme3M(R) cells showed an increased expression of pEGFRY845. CAGE and miR-217 inhibitor regulated the expression of pEGFRY845. CAGE showed interactions with EGFR and HER2 and regulated the in vivo sensitivity to trastuzumab. The down-regulation of EGFR or HER2 enhanced the sensitivity to anti-cancer drugs. CAGE showed direct regulation of HER2 and was necessary for the interaction between EGFR and HER2 in Malme3M(R) cells. miR-217 inhibitor induced interactions of CAGE with EGFR and HER2 in Malme3M cells. The inhibition of EGFR by CAGE-binding GTGKT peptide enhanced the sensitivity to gefitinib and trastuzumab and prevented interactions of EGFR with CAGE and HER2. Our results show that miR-217-CAGE feedback loop serves as a target for overcoming resistance to various anti-cancer drugs, including EGFR and HER2 inhibitors.
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약학대학 > 약학과 > Journal papers
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