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miR-378a-3p modulates tamoxifen sensitivity in breast cancer MCF-7 cells through targeting GOLT1A
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miR-378a-3p modulates tamoxifen sensitivity in breast cancer MCF-7 cells through targeting GOLT1A
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Journal Article
miR-378a-3p modulates tamoxifen sensitivity in breast cancer MCF-7 cells through targeting GOLT1A
2015
Overview
Breast cancer is a hormone-dependent cancer and usually treated with endocrine therapy using aromatase inhibitors or anti-estrogens such as tamoxifen. A majority of breast cancer, however, will often fail to respond to endocrine therapy. In the present study, we explored miRNAs associated with endocrine therapy resistance in breast cancer. High-throughput miRNA sequencing was performed using RNAs prepared from breast cancer MCF-7 cells and their derivative clones as endocrine therapy resistant cell models, including tamoxifen-resistant (TamR) and long-term estrogen-deprived (LTED) MCF-7 cells. Notably, miR-21 was the most abundantly expressed miRNA in MCF-7 cells and overexpressed in TamR and LTED cells. We found that miR-378a-3p expression was downregulated in TamR and LTED cells as well as in clinical breast cancer tissues. Additionally, lower expression levels of miR-378a-3p were associated with poor prognosis for tamoxifen-treated patients with breast cancer.
GOLT1A
was selected as one of the miR-378a-3p candidate target genes by
in silico
analysis.
GOLT1A
was overexpressed in breast cancer specimens and
GOLT1A
-specific siRNAs inhibited the growth of TamR cells. Low
GOLT1A
levels were correlated with better survival in patients with breast cancer. These results suggest that miR-378a-3p-dependent
GOLT1A
expression contributes to the mechanisms underlying breast cancer endocrine resistance.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Antineoplastic Agents, Hormonal - therapeutic use
/ Antineoplastic Agents, Hormonal - toxicity
/ Breast Neoplasms - drug therapy
/ Breast Neoplasms - mortality
/ Breast Neoplasms - pathology
/ Cell Survival - drug effects
/ Drug Resistance, Neoplasm - drug effects
/ Female
/ Gene Expression Regulation, Neoplastic - drug effects
/ High-Throughput Nucleotide Sequencing
/ Humanities and Social Sciences
/ Humans
/ MicroRNAs - antagonists & inhibitors
/ miRNA
/ RNA - isolation & purification
/ RNA, Double-Stranded - metabolism
/ RNA, Small Interfering - metabolism
/ Science
/ siRNA
/ Vesicular Transport Proteins - antagonists & inhibitors
