PDF(Pubmed)
Abstract：
Increasing numbers of long noncoding RNAs (lncRNAs) are implicated in breast cancer oncogenicity. However, the contribution of LINC02568 toward breast cancer progression remains unclear and requires further investigation. Herein, we evaluated LINC02568 expression in breast cancer and clarified its effect on disease malignancy. We also investigated the mechanisms underlying the pro-oncogenic role of LINC02568. Consequently, LINC02568 was upregulated in breast cancer samples, with a notable association with worse overall survival. Functionally, depleted LINC02568 suppressed cell proliferation, colony formation, and metastasis, whereas LINC02568 overexpression exerted the opposite effects. Our mechanistic investigations suggested that LINC02568 was physically bound to and sequestered microRNA-874-3p (miR-874-3p). Furthermore, miR-874-3p mediated suppressive effects in breast cancer cells by targeting cyclin E1 (CCNE1). LINC02568 positively controlled CCNE1 expression by sequestering miR-874-3p. Rescue experiments revealed that increased miR-874-3p or decreased CCNE1 expression recovered cell growth and motility functions induced by LINC02568 in breast cancer cells. In conclusion, the tumor-promoting functions of LINC02568 in breast cancer cells were enhanced by sequestering miR-874-3p and consequently over-expressing CCNE1. Our data may facilitate the identification of novel therapeutic targets in clinical settings.
摘要：
越来越多的长链非编码RNA（lncRNA）与乳腺癌的致癌作用有关。然而,LINC02568对乳腺癌进展的贡献尚不清楚,需要进一步研究.在这里，我们评估了LINC02568在乳腺癌中的表达,并阐明了其对疾病恶性程度的影响.我们还研究了LINC02568的原癌作用的潜在机制。因此,LINC02568在乳腺癌样本中上调，与较差的总生存率显著相关。功能上,耗尽的LINC02568抑制细胞增殖，菌落形成,和转移，而LINC02568过表达发挥相反的作用。我们的机制研究表明，LINC02568与microRNA-874-3p（miR-874-3p）物理结合并隔离。此外，miR-874-3p通过靶向细胞周期蛋白E1（CCNE1）介导乳腺癌细胞的抑制作用。LINC02568通过隔离miR-874-3p正控制CCNE1表达。挽救实验表明，增加的miR-874-3p或减少的CCNE1表达恢复了LINC02568在乳腺癌细胞中诱导的细胞生长和运动功能。总之,通过隔离miR-874-3p并因此过表达CCNE1,LINC02568在乳腺癌细胞中的肿瘤促进功能得到增强.我们的数据可能有助于在临床环境中识别新的治疗靶标。
