Dataset Information

MiR-1268b confers chemosensitivity in breast cancer by targeting ERBB2-mediated PI3K-AKT pathway.

ABSTRACT: Chemoresistance represents a major obstacle to effective therapy for breast cancer. Emerging evidences associated aberrantly expressed miRNAs with tumor development and chemoresistance. MiR-1268b has never been studied in any cancers before, and its roles in mediating tumor progression and drug resistance are still unclear. Selected from miRNA microarray and confirmed by real-time quantitative PCR (RT-qPCR), miR-1268b was found to be significantly upregulated in drug sensitive and ERBB2 negative tissues, as well as in breast cancer patients with low clinical stage. And miR-1268b had a higher expression in chemosensitive breast cancer cell lines, compared with the chemoresistant cell line. Moreover, the results revealed that miR-1268b induced breast cancer cell apoptosis and increased cell chemosensitivity. ERBB2 was demonstrated to be the target gene of miR-1268b by dual-luciferase reporter assays, western blot, and immunocytochemistry. Furthermore, PI3KCA, AKT, BCL2 in the ERBB2-PI3K-AKT signaling pathway were found to be downstream effectors of miR-1268b. In conclusion, miR-1268b increased chemosensitivity, at least in part, via modulation of PI3K-AKT pathway by targeting ERBB2. MiR-1268b may serve as a potential therapeutic target for patients with breast cancers.

SUBMITTER: Zhu WJ

PROVIDER: S-EPMC5685697 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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MiR-1268b confers chemosensitivity in breast cancer by targeting ERBB2-mediated PI3K-AKT pathway.

Zhu Wen-Jie WJ Chen Xu X Wang Ya-Wen YW Liu Hai-Ting HT Ma Ran-Ran RR Gao Peng P

Oncotarget 20170809 52

Chemoresistance represents a major obstacle to effective therapy for breast cancer. Emerging evidences associated aberrantly expressed miRNAs with tumor development and chemoresistance. MiR-1268b has never been studied in any cancers before, and its roles in mediating tumor progression and drug resistance are still unclear. Selected from miRNA microarray and confirmed by real-time quantitative PCR (RT-qPCR), miR-1268b was found to be significantly upregulated in drug sensitive and ERBB2 negative ...[more]

PMID: 29163776

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Project description:Proliferation is one of the significant hallmarks of gallbladder cancer, which is a relatively rare but fatal malignance. Aim of this study was to examine the biological impact and molecular mechanism of the candidate hub-gene on the proliferation and tumorigenesis of gallbladder cancer. We analyzed the differentially expressed genes and the correlation between these genes with MKI67, and showed that KIF11 is one of the major upregulated regulators of proliferation in gallbladder cancer (GBC). The Gene Ontology, Gene Sets Enrichment Analysis and KEGG Pathway analysis indicated that KIF11 may promote GBC cell proliferation through the ERBB2/PI3K/AKT signaling pathway. Gain-of-function and loss-of-function assay demonstrated that KIF11 regulated GBC cell cycle and cancer cell proliferation in vitro. GBC cells exhibited G2M phase cell cycle arrest, cell proliferation and clone formation ability reduction after treatment with Monastrol, a specific inhibitor of KIF11. Xenograft model showed that KIF11 promotes GBC growth in vivo. Rescue experiments showed that KIF11-induced GBC cell proliferation dependented on ERBB2/PI3K/AKT pathway. Moreover, we found that H3K27ac signals are enriched among the promoter region of KIF11 in the UCSC Genome Browser Database. Differentially expressed analysis showed that EP300, a major histone acetyltransferase modifying H3K27ac signal, is highly expressed in gallbladder cancer and correlation analysis illustrated that EP300 is positively related with KIF11 in almost all the cancer types. We further found that KIF11 was significantly downregulated in a dose-dependent and time-dependent manner after histone acetylation inhibitor treatment. The present results highlight that high KIF11 expression promotes GBC cell proliferation through the ERBB2/PI3K/AKT signaling pathway. The findings may help deepen our understanding of mechanism underlying GBC cancer development and development of novel diagnostic and therapeutic target.

Dataset Information

MiR-1268b confers chemosensitivity in breast cancer by targeting ERBB2-mediated PI3K-AKT pathway.

Publications

MiR-1268b confers chemosensitivity in breast cancer by targeting ERBB2-mediated PI3K-AKT pathway.

Similar Datasets

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