Department of Oncology, Shandong Provincial Chest Hospital, Jinan, Shandong, China.
Department of Orthopedics, Dongying Shengli Hospital, Dongying, Shandong, China.
Biochem Biophys Res Commun. 2021 Apr 9;548:112-119. doi: 10.1016/j.bbrc.2021.02.072. Epub 2021 Feb 25.
Long noncoding RNAs (lncRNAs) have been identified as functional modulators in human tumors. The purpose of our study was to determine the expressing trend, clinical significance and functions of lncRNA LINC02381(LINC02381) in osteosarcoma. We observed that the expression of LINC02381 and cell division cycle-associated protein 4 (CDCA4) were distinctly increased in osteosarcoma specimens and cells, while miR-503-5p expression was decreased. Additionally, ETS transcription factor ELK1 (ELK1) could bind directly to the LINC02381 promoter region and activate its transcription. Clinical assays revealed that high LINC02381 was associated with advanced clinical progress and poor clinical outcome. Functionally, knockdown of LINC02381 suppressed the proliferation, migration and invasion of osteosarcoma cells. What's more, LINC02381 could down-regulate CDCA4 via sponging miR-503-5p, and there existed a negative correlation between LINC02381 expression and miR-503-5p expression in 92 osteosarcoma samples. Rescue experiments proved the carcinogenic role of LINC02381/miR-503-5p/CDCA4 axis in osteosarcoma progression. Overall, our data illustrated how LINC02381 played an oncogenic role in osteosarcoma and might offer a novel diagnostic and prognostic biomarker and potential therapeutic target for osteosarcoma.
长链非编码 RNA(lncRNA)已被鉴定为人类肿瘤中的功能调节剂。我们的研究目的是确定 lncRNA LINC02381(LINC02381)在骨肉瘤中的表达趋势、临床意义和功能。我们观察到 LINC02381 和细胞分裂周期相关蛋白 4(CDCA4)的表达在骨肉瘤标本和细胞中明显增加,而 miR-503-5p 的表达降低。此外,ETS 转录因子 Elk1(ELK1)可以直接结合到 LINC02381 的启动子区域并激活其转录。临床检测表明,高表达的 LINC02381 与晚期临床进展和不良临床结局相关。功能上,敲低 LINC02381 抑制骨肉瘤细胞的增殖、迁移和侵袭。更重要的是,LINC02381 可以通过海绵吸附 miR-503-5p 来下调 CDCA4,并且在 92 例骨肉瘤样本中 LINC02381 的表达与 miR-503-5p 的表达呈负相关。挽救实验证明了 LINC02381/miR-503-5p/CDCA4 轴在骨肉瘤进展中的致癌作用。总体而言,我们的数据说明了 LINC02381 如何在骨肉瘤中发挥致癌作用,并可能为骨肉瘤提供新的诊断和预后生物标志物以及潜在的治疗靶点。