Luan Tian, Zhang Ximei, Wang Shuyuan, Song Yan, Zhou Shunheng, Lin Jing, An Weiwei, Yuan Weiguang, Yang Yue, Cai Huilong, Zhang Qingyuan, Wang Lihong
Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin Medical University, Harbin 150081, China.
Department of Histology and Embryology, Harbin Medical University, Harbin 150081, China.
Oncotarget. 2017 Jul 12;8(44):76153-76164. doi: 10.18632/oncotarget.19190. eCollection 2017 Sep 29.
Long non-coding RNAs (lncRNA) have been reported as key regulators in the progression and metastasis of breast cancer. In this study, we found that the lncRNA myocardial infarction associated transcript (MIAT) expression was upregulated in breast cancer in The Cancer Genome Atlas (TCGA) data sets. We validated that MIAT was higher in breast cancer cell lines and advanced breast tumors than in normal controls. And MIAT overexpression associated with TNM stage and lymphnode metastasis. Knockdown MIAT inhibited breast cancer cell proliferation and promoted apoptosis. Also MIAT downregulation suppressed epithelial-mesenchymal transition (EMT) and decreased migration and invasion in MDA-MB-231 and MCF-7 breast cancer cell lines. More importantly, knockdown MIAT inhibited tumor growth . Our results suggested that MIAT acted as a competing endogenous RNA (ceRNA) to regulate the expression of dual specificity phosphatase 7 (DUSP7) by taking up miR-155-5p in breast cancer. There were positive correlation between MIAT and DUSP7 expression in breast cancer patients. We conclude that MIAT promotes breast cancer progression and functions as ceRNA to regulate DUSP7 expression by sponging miR-155-5p in breast cancer.
长链非编码RNA(lncRNA)已被报道为乳腺癌进展和转移中的关键调节因子。在本研究中,我们发现在癌症基因组图谱(TCGA)数据集中,lncRNA心肌梗死相关转录本(MIAT)在乳腺癌中的表达上调。我们验证了MIAT在乳腺癌细胞系和晚期乳腺肿瘤中比在正常对照中更高。并且MIAT过表达与TNM分期和淋巴结转移相关。敲低MIAT可抑制乳腺癌细胞增殖并促进细胞凋亡。此外,MIAT下调可抑制上皮-间质转化(EMT),并降低MDA-MB-231和MCF-7乳腺癌细胞系的迁移和侵袭能力。更重要的是,敲低MIAT可抑制肿瘤生长。我们的结果表明,在乳腺癌中,MIAT作为一种竞争性内源RNA(ceRNA),通过结合miR-155-5p来调节双特异性磷酸酶7(DUSP7)的表达。在乳腺癌患者中,MIAT与DUSP7表达之间存在正相关。我们得出结论,MIAT促进乳腺癌进展,并作为ceRNA通过在乳腺癌中吸附miR-155-5p来调节DUSP7表达。