Exosome-mediated transfer of lncRNA‑SNHG14 promotes trastuzumab chemoresistance in breast cancer

International Journal of Oncology
Huaying DongJing Han

Abstract

Currently, resistance to trastuzumab, a human epidermal growth factor receptor 2 (HER2) inhibitor, has become an important obstacle to improving the clinical outcome of patients with advanced HER2+ breast cancer. While cell behavior may be modulated by long non‑coding RNAs (lncRNAs), the contributions of lncRNAs within extracellular vesicles (exosomes) are largely unknown. To this end, the involvement and regulatory functions of potential lncRNAs contained within exosomes during the formation of chemoresistance in human breast cancer were investigated. Trastuzumab-resistant cell lines were established by continuously grafting HER2+ SKBR-3 and BT474 cells into trastuzumab-containing culture medium. An lncRNA microarray assay followed by reverse transcription‑quantitative polymerase chain reaction analysis identified that lncRNA-small nucleolar RNA host gene 14 (SNHG14) was upregulated in trastuzumab-resistant cells when compared with parental breast cancer cells. Functional experimentation demonstrated that knockdown of lncRNA‑SNHG14 potently promoted trastuzumab-induced cytotoxicity. Furthermore, extracellular lncRNA‑SNHG14 was able to be incorporated into exosomes and transmitted to sensitive cells, thus disseminating trastuzu...Continue Reading

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Methods Mentioned

BETA
RNA Assay
transfection
fluorescence microscopy
Protein Assay
transmission electron microscopy
flow cytometry
xenograft

Software Mentioned

Cluster
Agilent Gene Spring
SPSS
MedCalc
NTA

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