Department of Second Breast Surgery, Jilin Cancer Hospital, Jilin, 130012, China.
Department of Medical Insurance Guarantee Office, Jilin Cancer Hospital, Jilin, 130012, China.
Oncol Res. 2022 Aug 31;29(4):291-303. doi: 10.32604/or.2022.025172. eCollection 2021.
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.
越来越多的长链非编码 RNA(lncRNA)被认为与乳腺癌致癌性有关。然而,LINC02568 对乳腺癌进展的贡献尚不清楚,需要进一步研究。在此,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 致癌作用的潜在机制。结果表明,LINC02568 在乳腺癌样本中上调,与总体生存率显著相关。功能上,LINC02568 缺失抑制细胞增殖、集落形成和转移,而过表达则产生相反的效果。我们的机制研究表明,LINC02568 与 microRNA-874-3p(miR-874-3p)物理结合并将其隔离。此外,miR-874-3p 通过靶向细胞周期蛋白 E1(CCNE1)对乳腺癌细胞发挥抑制作用。LINC02568 通过隔离 miR-874-3p 正向调控 CCNE1 表达。挽救实验表明,增加 miR-874-3p 或降低 CCNE1 表达可恢复 LINC02568 诱导的乳腺癌细胞生长和迁移功能。总之,LINC02568 通过隔离 miR-874-3p 并进而过表达 CCNE1,增强了其在乳腺癌细胞中的促肿瘤功能。我们的数据可能有助于在临床环境中确定新的治疗靶点。