Jun Fang1, Kun Li2,3, Chen Huang1, Huimin Xue1, Qichao Ni1. 1. Department of General Surgery, Affiliated Hospital of Nantong University Nantong 226001, Jiangsu, PR China. 2. Department of Thyroid and Breast Surgery, Kunshan Hospital of Traditional Chinese Medicine Kunshan 215300, Jiangsu, PR China. 3. Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine Kunshan 215300, Jiangsu, PR China.
Abstract
OBJECTIVE: Tamoxifen resistance of breast cancer (BC) is a significant hindrance in clinical therapy. The long-noncoding RNA (lncRNA) TTN-AS1 has been reported as a crucial tumor promoting factor in various cancers. In this study, we set out to discover the specific pathologic regulatory mechanisms of tamoxifen-resistance in breast cancer. METHODS: MTT assay was conducted to evaluate the cell viability of the breast cancer cell lines MCF-7 and MCF-7/TAM. QRT-PCR and western blot assay were performed to estimate the expression of TTN-AS1, miR-107 and related proteins. Flow cytometry was conducted to identify degree of apoptosis and cell cycle. The invasive ability was estimated by transwell chamber assay. RESULTS: Our findings revealed that TTN-AS1 can enhance tamoxifen-resistance in BC cells and augment the invasive ability of tamoxifen-resistant breast cancer cells by down-regulating miR-107, and thereby encourage the development of drug-resistant BC. Further investigation indicates that lncRNA TTN-AS1 worsens the course of tamoxifen-resistant BC by regulating zinc and ring finger 2 (ZNRF2) via miR-107 and activating the PI3K/AKT pathway. CONCLUSION: Our findings suggest that the lncRNA TTN-AS1 can encourage tamoxifen-resistance in BC by modulating the miR-107/ZNRF2 axis and stimulating the PI3K/AKT pathway. AJTR
OBJECTIVE: Tamoxifen resistance of breast cancer (BC) is a significant hindrance in clinical therapy. The long-noncoding RNA (lncRNA) TTN-AS1 has been reported as a crucial tumor promoting factor in various cancers. In this study, we set out to discover the specific pathologic regulatory mechanisms of tamoxifen-resistance in breast cancer. METHODS: MTT assay was conducted to evaluate the cell viability of the breast cancer cell lines MCF-7 and MCF-7/TAM. QRT-PCR and western blot assay were performed to estimate the expression of TTN-AS1, miR-107 and related proteins. Flow cytometry was conducted to identify degree of apoptosis and cell cycle. The invasive ability was estimated by transwell chamber assay. RESULTS: Our findings revealed that TTN-AS1 can enhance tamoxifen-resistance in BC cells and augment the invasive ability of tamoxifen-resistant breast cancer cells by down-regulating miR-107, and thereby encourage the development of drug-resistant BC. Further investigation indicates that lncRNA TTN-AS1 worsens the course of tamoxifen-resistant BC by regulating zinc and ring finger 2 (ZNRF2) via miR-107 and activating the PI3K/AKT pathway. CONCLUSION: Our findings suggest that the lncRNA TTN-AS1 can encourage tamoxifen-resistance in BC by modulating the miR-107/ZNRF2 axis and stimulating the PI3K/AKT pathway. AJTR
Authors: Guojun Wu; Mingzhao Xing; Elizabeth Mambo; Xin Huang; Junwei Liu; Zhongmin Guo; Aditi Chatterjee; David Goldenberg; Susanne M Gollin; Saraswati Sukumar; Barry Trink; David Sidransky Journal: Breast Cancer Res Date: 2005-05-31 Impact factor: 6.466