Long non-coding RNA SNHG14 induces trastuzumab resistance of breast cancer via regulating PABPC1 expression through H3K27 acetylation.

Abstract

Currently, resistance to trastuzumab, a human epidermal growth factor receptor 2 (HER2) inhibitor, has become one major obstacle for improving the clinical outcome of patients with advanced HER2+ breast cancer. While cell behaviour can be modulated by long non-coding RNAs (lncRNAs), the contributions of lncRNAs in progression and trastuzumab resistance of breast cancer are largely unknown. To this end, the involvement and regulatory functions of lncRNA SNHG14 in human breast cancer were investigated. RT-qPCR assay showed that SNHG14 was up-regulated in breast cancer tissues and associated with trastuzumab response. Gain- and loss-of-function experiments revealed that overexpression of SNHG14 promotes cell proliferation, invasion and trastuzumab resistance, whereas knockdown of SNHG14 showed an opposite effect. PABPC1 gene was identified as a downstream target of SNHG14, and PABPC1 mediates the SNHG14-induced oncogenic effects. More importantly, ChIP assays demonstrated that lncRNA SNHG14 may induce PABPC1 expression through modulating H3K27 acetylation in the promoter of PABPC1 gene, thus resulting in the activation of Nrf2 signalling pathway. These data suggest that lncRNA SNHG14 promotes breast cancer tumorigenesis and trastuzumab resistance through regulating PABPC1 expression through H3K27 acetylation. Therefore, SNHG14 may serve as a novel diagnostic and therapeutic target for breast cancer patients.

• Authors: Huaying Dong, Wei Wang, Shaowei Mo, Qiang Liu, Xin Chen, Ru Chen, Yu Zhang, Kejian Zou, Mulin Ye, Xionghui He, Fan Zhang, Jing Han, Jianguo Hu
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 22 Issue 10 Pg. 4935-4947 (10 2018) ISSN: 1582-4934 [Electronic] England
• PMID: 30063126 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Poly(A)-Binding Protein I
• RNA, Long Noncoding
• SNHG16 lncRNA, human
• Jumonji Domain-Containing Histone Demethylases
• KDM6B protein, human
• Trastuzumab

Topics

• Acetylation (drug effects)
• Adult
• Aged
• Aged, 80 and over
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Resistance, Neoplasm
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Jumonji Domain-Containing Histone Demethylases (genetics)
• Middle Aged
• NF-E2-Related Factor 2 (genetics)
• Poly(A)-Binding Protein I (genetics)
• Promoter Regions, Genetic (drug effects)
• RNA, Long Noncoding (genetics)
• Signal Transduction (drug effects)
• Trastuzumab (administration & dosage, adverse effects)