Department of Chinese and Western Μedicine Οrthopedics of 31 Ward, Loudi Central Hospital, Loudi, Hunan 417000, P.R. China.
Oncol Rep. 2018 Mar;39(3):1072-1080. doi: 10.3892/or.2018.6182. Epub 2018 Jan 3.
Increasing evidence indicates that long non‑coding RNAs (lncRNAs) play an important role in multiple biological processes including cell growth, differentiation, proliferation and invasion. Urothelial carcinoma associated 1 (UCA1) is a highly conserved nuclear ncRNA and a key regulator of cell proliferation and apoptosis in several types of cancers. However, its role in osteosarcoma progression is not well known. In the present study, we aimed to determine the biological role of UCA1 in osteosarcoma progression. RT‑qPCR analysis showed that UCA1 expression was significantly increased in osteosarcoma cell lines and promoted cell growth in osteosarcoma. We then sought to determine the mechanism underlying the upregulation of UCA1 in osteosarcoma. Luciferase reporter assay and chromatin immunoprecipitation assay suggested that lncRNA UCA1 was induced by HIF‑1α and HIF‑1α interacts with the HIF‑1α response element in the promoter region of UCA1. In addition, the gain- and loss-of-functional assay showed that HIF‑1α promoted osteosarcoma cell growth through inducing the UCA1 expression level. More importantly, Cignal Signal Transduction Reporter Array and western blot assay showed that lncRNA UCA1 inactivated the PTEN/AKT signaling pathway. Finally, we observed that HIF‑1α induced cell growth through the UCA1/PTEN/AKT signaling pathway. To conclude, our integrated approach demonstrates that UCA1 confers a tumor promoter function by promoting cell proliferation and silencing of the PTEN/AKT signaling pathway in osteosarcoma. Thus, UCA1 can serve as a promising therapeutic target for osteosarcoma patients.
越来越多的证据表明，长非编码 RNA（lncRNA）在多种生物学过程中发挥着重要作用，包括细胞生长、分化、增殖和侵袭。尿路上皮癌相关 1（UCA1）是一种高度保守的核非编码 RNA，是多种癌症中细胞增殖和凋亡的关键调节因子。然而，其在骨肉瘤进展中的作用尚不清楚。在本研究中，我们旨在确定 UCA1 在骨肉瘤进展中的生物学作用。实时定量 PCR 分析显示，UCA1 在骨肉瘤细胞系中的表达显著增加，并促进骨肉瘤细胞的生长。然后，我们试图确定骨肉瘤中 UCA1 上调的机制。荧光素酶报告基因分析和染色质免疫沉淀分析表明，lncRNA UCA1 由 HIF-1α 诱导，HIF-1α 与 UCA1 启动子区域的 HIF-1α 反应元件相互作用。此外，增益和缺失功能测定表明，HIF-1α 通过诱导 UCA1 表达水平促进骨肉瘤细胞生长。更重要的是，Cignal Signal Transduction Reporter Array 和 Western blot 分析表明，lncRNA UCA1 使 PTEN/AKT 信号通路失活。最后，我们观察到 HIF-1α 通过 UCA1/PTEN/AKT 信号通路诱导细胞生长。总之，我们的综合方法表明，UCA1 通过促进骨肉瘤细胞增殖和沉默 PTEN/AKT 信号通路发挥肿瘤促进功能。因此，UCA1 可以作为骨肉瘤患者有前途的治疗靶点。
