南方医科大学学报2017，Vol.37Issue(11)：1427-1435,9.DOI:10.3969/j.issn.1673-4254.2017.11.01
生长停滞特异性转录本5在乳腺癌中低表达并抑制上皮细胞-间充质转化
Low expression of lncRNA-GAS5 promotes epithelial-mesenchymal transition of breast cancer cells in vitro
摘要
Abstract
Objective To investigate the role of long non-coding RNA growth arrest-specific transcript 5 (lncRNA-GAS5) in breast cancer progression and epithelial-mesenchymal transition (EMT) of the cancer cells. Methods Real-time quantitative PCR (qRT-PCR) was used to detect the expression of lncRNA-GAS5 in 37 pairs of breast cancer and adjacent non-tumor tissues and in parental MCF-7 cells and paclitaxel-resistant MCF-7 (MCF-7/PR) cells, and the correlation of lncRNA-GAS5 expression with the clinical stage and lymph node metastasis of breast cancer was investigated. The expressions of the genes related with cell cycle and EMT at both the mRNA and protein levels were detected using qRT-PCR, Western blotting and immunohistochemistry. The changes in the biological behaviors and morphology of breast cancer cells with either lncRNA-GAS5 knockdown or overexpression were observed. Nude mouse models were established bearing breast cancer xenografts derived from MCF-7/PR cells or MCF-7/PR cells over-expressing lncRNA-GAS5, and the inhibitory effect of paclitaxel on tumor growth was evaluated. Results The transcriptional levels of lncRNA-GAS5 were significantly lower in breast cancer tissues than in the adjacent non-tumor tissues (P<0.05), and decreased lncRNA-GAS5 expression was significantly correlated with TNM stage and lymph node metastasis of breast cancer (P<0.05). lncRNA-GAS5 expression was also significantly lowered in paclitaxel-resistant breast cancer cells and showed a positive correlation with P21 expression and a negative correlation with CDK6. MCF-7 cells during EMT presented with a lowered expression of lncRNA-GAS5, whereas lncRNA-GAS5 over-expression strongly suppressed MCF-7/PR cell migration and invasion, and increased the susceptibility of the cells to paclitaxel. In the tumor-bearing nude mouse models, lncRNA-GAS5 overexpression in the tumor cells obviously enhanced the inhibitory effect of paclitaxel on tumor growth and lung metastasis by reversing the EMT marker proteins. Conclusion A decreased expression of lncRNA-GAS5 promotes lung metastasis of breast cancer by inducing EMT, suggesting the potential of lncRNA-GAS5 as a therapeutic target in breast cancer.关键词
长链非编码RNA/生长停滞特异性转录本5/乳腺癌/上皮细胞-间充质转化Key words
long non-coding RNA/growth arrest-specific transcript 5/breast cancer/epithelial-mesenchymal transition引用本文复制引用
丁勇兴,段克才,陈素莲..生长停滞特异性转录本5在乳腺癌中低表达并抑制上皮细胞-间充质转化[J].南方医科大学学报,2017,37(11):1427-1435,9.基金项目
安徽省教育厅自然科学重大项目(KJ2015ZD29, KJ2016SD37) （KJ2015ZD29, KJ2016SD37）
安徽省自然科学基金(1508085MH159) （1508085MH159）
安徽省高校学科(专业)拔尖人才学术资助重点项目(gxbjZD2016069) （专业）
安徽省蚌埠市科技计划项目(20150309) （20150309）
