Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, New York, USA.
Molecular and Cellular Biology Program, Stony Brook University, Stony Brook, NY, 11794, USA.
Nat Commun. 2020 Dec 22;11(1):6438. doi: 10.1038/s41467-020-20207-y.
Misregulation of long non-coding RNA (lncRNA) genes has been linked to a wide variety of cancer types. Here we report on Mammary Tumor Associated RNA 25 (MaTAR25), a nuclear enriched and chromatin associated lncRNA that plays a role in mammary tumor cell proliferation, migration, and invasion, both in vitro and in vivo. MaTAR25 functions by interacting with purine rich element binding protein B (PURB), and associating with a major downstream target gene Tensin1 (Tns1) to regulate its expression in trans. The Tns1 protein product is a critical component of focal adhesions linking signaling between the extracellular matrix and the actin cytoskeleton. Knockout of MaTAR25 results in down-regulation of Tns1 leading to a reorganization of the actin cytoskeleton, and a reduction of focal adhesions and microvilli. We identify LINC01271 as the human ortholog of MaTAR25, and importantly, increased expression of LINC01271 is associated with poor patient prognosis and metastasis. Our findings demonstrate that LINC01271 represents a potential therapeutic target to alter breast cancer progression.
长链非编码 RNA（lncRNA）基因的失调与多种癌症类型有关。在这里，我们报告了一种称为乳腺肿瘤相关 RNA 25（MaTAR25）的核富集和染色质相关 lncRNA，它在体外和体内都在乳腺肿瘤细胞的增殖、迁移和侵袭中发挥作用。MaTAR25 通过与富含嘌呤的元件结合蛋白 B（PURB）相互作用，并与主要下游靶基因 Tensin1（Tns1）结合，在转录水平上调节其表达。Tns1 蛋白产物是连接细胞外基质和肌动蛋白细胞骨架之间信号的焦点粘连的关键组成部分。MaTAR25 的敲除导致 Tns1 的下调，从而导致肌动蛋白细胞骨架的重新组织，焦点粘连和微绒毛减少。我们确定 LINC01271 是 MaTAR25 的人类同源物，重要的是，LINC01271 的表达增加与患者预后不良和转移有关。我们的研究结果表明，LINC01271 代表了改变乳腺癌进展的潜在治疗靶标。
