Department of Orthopaedics, Minhang Hospital, Fudan University, 170 Xin-Song Road, Shanghai 201199, China.
Biomed Res Int. 2020 Sep 9;2020:1974506. doi: 10.1155/2020/1974506. eCollection 2020.
Osteosarcoma is a malignant tumor that seriously threatens human health. Numerous studies have pointed out the potential of long noncoding RNAs (lncRNAs) as new therapeutic targets for various human cancers. Therefore, we mainly investigate whether there is a new type of lncRNA pathway involved in regulating the development of osteosarcoma. The present study shows the higher expression levels of LINC00511 correlates to a shorter overall survival and disease-free survival time in patients with sarcoma. It is significantly higher in the clinical samples of osteosarcoma patients than in normal adjacent cancer tissues. We used U373 and SW1353 osteosarcoma cells to determine the effect of lncRNA on osteosarcoma proliferation and invasion by knocking down LINC00511 compared with controls. The results showed that the LINC00511 knockdown significantly suppressed osteosarcoma cell growth and metastasis. To explore the mechanisms of LINC00511 in osteosarcoma, we tested whether LINC00511 could competitively stimulate miR-185-3p and regulate E2F1 as a ceRNA. The results showed that LINC00511 knockdown induced the increased level of miR-185-3p levels; however, miR-185-3p overexpression suppressed LINC00511 levels. In addition, the results also demonstrated that LINC00511 knockdown or miR-185-3p overexpression could reduce E2F1 levels in osteosarcoma cells. The dual-luciferase reporter assay verified the direct interaction between miR-185-3p and LINC00511 or E2F1. These results may offer an explanation of how the lncRNA affects the progression of osteosarcoma, and our study shows that LINC00511 can be a novel biomarker in osteosarcoma.
骨肉瘤是一种严重威胁人类健康的恶性肿瘤。大量研究指出长链非编码 RNA（lncRNA）作为多种人类癌症新的治疗靶点的潜力。因此，我们主要研究是否存在涉及调节骨肉瘤发生的新型 lncRNA 通路。本研究表明，LINC00511 的高表达水平与肉瘤患者的总生存期和无病生存期较短相关。在骨肉瘤患者的临床样本中，其表达水平明显高于正常相邻癌组织。我们使用 U373 和 SW1353 骨肉瘤细胞，通过与对照组相比，敲低 LINC00511 来确定 lncRNA 对骨肉瘤增殖和侵袭的影响。结果表明，LINC00511 的敲低显著抑制骨肉瘤细胞的生长和转移。为了探讨 LINC00511 在骨肉瘤中的作用机制，我们测试了 LINC00511 是否可以竞争性地刺激 miR-185-3p 并作为 ceRNA 调节 E2F1。结果表明，LINC00511 的敲低诱导 miR-185-3p 水平增加；然而，miR-185-3p 的过表达抑制了 LINC00511 的水平。此外，结果还表明，LINC00511 的敲低或 miR-185-3p 的过表达可以降低骨肉瘤细胞中的 E2F1 水平。双荧光素酶报告基因实验验证了 miR-185-3p 与 LINC00511 或 E2F1 之间的直接相互作用。这些结果可能解释了 lncRNA 如何影响骨肉瘤的进展，我们的研究表明 LINC00511 可以作为骨肉瘤的一种新型生物标志物。
