Dataset Information

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

ABSTRACT: MicroRNA array analysis revealed that miR-217 expression was decreased in anti-cancer drug-resistant Malme3MR 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 Malme3MR 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 Malme3MR 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.

SUBMITTER: Kim Y

PROVIDER: S-EPMC4891121 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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

Kim Youngmi Y Kim Hyuna H Park Deokbum D Han Minho M Lee Hansoo H Lee Yun Sil YS Choe Jongseon J Kim Young Myeong YM Jeoung Dooil D

Oncotarget 20160301 9

MicroRNA array analysis revealed that miR-217 expression was decreased in anti-cancer drug-resistant Malme3MR 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, angiogeni ...[more]

PMID: 26863629

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Dataset Information

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

Publications

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

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