LINC00461 promotes cell migration and invasion in breast cancer through miR-30a-5p/integrin β3 axis
LINC00461 promotes cell migration and invasion in breast cancer through miR-30a-5p/integrin β3 axis
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DOI：
10.1002/jcb.27435
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发表时间：
2019-04-01
影响因子：
4
通讯作者：
Long, Jingpei
中科院分区：
文献类型：
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作者：
Dong, Lifeng;Qian, Junbin;Long, Jingpei
越来越多的证据表明，长非编码RNA(Long Non Coding RNAs，LncRNAs)在多种人类恶性肿瘤的发生、发展中起着调控作用。LINC00461是一种新的肿瘤相关基因，已被报道在脑胶质瘤中高表达并作为癌基因，但其在乳腺癌(BC)中的生物学作用尚不清楚。本研究旨在探讨LINC00461在BC中的作用，并阐明其可能的分子机制。在目前的研究中，发现LINC00461在BC组织和细胞系中都显著上调。此外，我们还发现LINC00461的高表达与肿瘤的TNM分期和分化程度有关。此外，功能研究表明，LINC00461可加速BC细胞的迁移和侵袭。值得注意的是，LINC00461可以促进波形蛋白和锌指E-box结合同源异型盒因子1的表达，抑制E-钙粘蛋白的表达，促进细胞外信号调节激酶和AKT信号通路的激活。力学研究表明，LINC00461以miR-30a-5p海绵形式正向调控整合素β3(ITGB3)在BC细胞中的表达。综上所述，LINC00461通过miR-30a-5p/ITGB3轴在BC中发挥致癌作用。我们的数据表明，LINC00461可能被用来作为一种新的候选治疗靶点和一个有价值的BC的诊断生物标志物。
Mounting evidence has demonstrated that long noncoding RNAs (lncRNAs) are dysregulated and implicated in the occurrence and development of a wide range of human malignancies. LINC00461, a novel cancer-related lncRNA, has been reported to be highly expressed and serve as oncogene in glioma; however, its biological role in breast cancer (BC) remains obscure. This study aimed to explore the role of LINC00461 in BC and elucidate the potential molecular mechanisms involved. In the current study, LINC00461 was found to be significantly upregulated in both BC tissues and cell lines. Besides, we found that high LINC00461 expression was associated with TNM stage and differentiation. Furthermore, functional studies demonstrated that LINC00461 expedited BC cell migration and invasion. Notably, LINC00461 was observed to enhance the expression of vimentin and zinc-finger E-box binding homeobox factor 1, suppress the expression of E-cadherin, and promote the activation of extracellular signal-regulated kinase and AKT signaling pathways. Mechanical investigations revealed that LINC00461 positively modulated integrin beta 3 (ITGB3) expression as miR-30a-5p sponge in BC cells. Taken together, LINC00461 exerts an oncogenic role in BC through miR-30a-5p/ITGB3 axis. Our data indicate that LINC00461 may be used to be a novel candidate therapeutic target and a valuable diagnostic biomarker for BC.