Abstract
This study aimed to investigate the roles and possible molecular mechanisms of long non-coding RNA HOTAIR in regulating resistance to trastuzumab in breast cancer. Trastuzumab-resistant breast cancer cell line SK-BR-3-TR was assayed for the expression of HOX antisense intergenic RNA (HOTAIR), epithelial-mesenchymal transition (EMT)-related proteins or genes. Methylation levels of TGF- β, PTEN and cyclin-dependent kinase inhibitor 1B (or P27) were determined. In trastuzumab-resistant cell line, the mRNA level of HOTAIR was significantly up-regulated; in addition, the expression of TGF-β, Snail and Vimentin was also up-regulated, E-cadherin was down-regulated while the expression of HER2, PI3K, AKT, mTOR and MAPK in the HER2 receptor pathway and phosphorylation level of HER2 receptor remained unchanged, the methylation levels of the PTEN gene and TGF-β were increased and decreased, respectively. RNA interference downregulated the HOTAIR level and sensitized the cells to trastuzumab. It also resulted in down-regulation of TGF-β, Snail, Vimentin, p-AKT, p-APK and CyclinD1 and up-regulation of E-cadherin, PTEN and P27. Besides, the methylation levels of the PTEN gene and TGF-β were reduced and increased, respectively. Mouse models grafted with SK-BR-3-TR grew faster than with SK-BR-3-TS and siHOTAIR-SK-BR-3-TR.
Highlights
This study aimed to investigate the roles and possible molecular mechanisms of long non-coding RNA HOTAIR in regulating resistance to trastuzumab in breast cancer
After several rounds of culture and selection, a stable trastuzumab resistant cell line SK-BR-3-TR was obtained (Fig. 1), which could grew stably in medium containing 8 μg/ ml trastuzumab which was over 10 times the level that trastuzumab-sensitive cells can tolerate
The lentivirus vector used for HOTAIR knockdown contained green fluorescent protein (GFP)
Summary
This study aimed to investigate the roles and possible molecular mechanisms of long non-coding RNA HOTAIR in regulating resistance to trastuzumab in breast cancer. Li et al found that in human laryngeal squamous cell carcinoma model HOTAIR induces the methylation and down-regulation of PTEN, leading to increased PI3K/ AKT pathway activity and proliferation and metastasis of cancer cells[8]. It is still unclear whether there is a similar regulatory mechanism in breast cancer. To better understand the molecular mechanism of trastuzumab resistance with regarding to HOTAIR, we investigated the expression and activity of genes in the HER2 receptor pathway and EMT- related TGF-β pathway These findings would provide clues to new treatment targets and strategies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
