Department of Breast, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Laboratory of Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.
J Cell Biochem. 2019 Apr;120(4):4851-4862. doi: 10.1002/jcb.27435. Epub 2019 Jan 8.
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 β3 (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.
越来越多的证据表明，长非编码 RNA（lncRNA）失调并参与广泛的人类恶性肿瘤的发生和发展。LINC00461 是一种新型的癌症相关 lncRNA，已被报道在神经胶质瘤中高表达并作为癌基因发挥作用；然而，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，并阐明其潜在的分子机制。在本研究中，发现 LINC00461 在 BC 组织和细胞系中均显著上调。此外，我们发现高表达 LINC00461 与 TNM 分期和分化有关。此外，功能研究表明 LINC00461 加速了 BC 细胞的迁移和侵袭。值得注意的是，LINC00461 被观察到增强波形蛋白和锌指 E-框结合同源盒因子 1 的表达，抑制 E-钙粘蛋白的表达，并促进细胞外信号调节激酶和 AKT 信号通路的激活。机制研究表明，LINC00461 作为 BC 细胞中的 miR-30a-5p 海绵正向调节整合素 β3（ITGB3）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 可能被用作 BC 的新型候选治疗靶点和有价值的诊断生物标志物。
