Zhao Weidong, Li Li
Food Nutrition Center, West China Hospital, Sichuan University, Chengdu, 610041, No. 37, Guoxue Xiang, Wuhou District, Sichuan, China.
Department of Lymphoma, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chendu, 610041, No. 55 Section 4 South Renmin Road, Sichuan, China.
Pathol Res Pract. 2019 Mar;215(3):439-445. doi: 10.1016/j.prp.2018.12.006. Epub 2018 Dec 10.
Long non-coding RNAs (LncRNAs) are acknowledged as crucial regulators in tumorigenesis and tumor progression. In this study, we explored the mechanism and function of lncRNA HCP5 in osteosarcoma (OS). At first, five lncRNAs were chosen from GeneCard and subjected to qRT-PCR examination. The results indicated that HCP5 was significantly overexpressed in four OS cell lines. Northern blot assay further proved the higher expression of HCP5 in OS cell lines. To identify the biological role of HCP5 in OS, we silenced the expression of HCP5 in U2OS and MG-63 cells which possessed the highest level of HCP5. CCK-8 and colony formation assay revealed the inhibitory effect of HCP5 knockdown on cell proliferation. Cell apoptosis was found to be increased in cells transfected with sh-HCP5#1. Moreover, cell invasion and epithelial-mesenchymal transition (EMT) were reversed by the silencing of HCP5. The results of functional assays showed that HCP5 acted as an oncogene in osteosarcoma. Mechanically, HCP5 was found to be activated by the transcription factor SP1. Finally, rescue assays were conducted to demonstrate the function of SP1/HCP5 axis in osteosarcoma. In conclusion, we confirmed that SP1-induced upregulation of long non-coding RNA HCP5 promotes the development of osteosarcoma.
长链非编码RNA（LncRNAs）被认为是肿瘤发生和肿瘤进展中的关键调节因子。在本研究中，我们探讨了lncRNA HCP5在骨肉瘤（OS）中的作用机制和功能。首先，从GeneCard中选取了5种lncRNAs并进行qRT-PCR检测。结果表明，HCP5在4种OS细胞系中显著高表达。Northern印迹分析进一步证实了HCP5在OS细胞系中的高表达。为了确定HCP5在OS中的生物学作用，我们在HCP5水平最高的U2OS和MG-63细胞中沉默了HCP5的表达。CCK-8和集落形成试验显示HCP5敲低对细胞增殖有抑制作用。发现转染sh-HCP5#1的细胞凋亡增加。此外，HCP5的沉默逆转了细胞侵袭和上皮-间质转化（EMT）。功能试验结果表明，HCP5在骨肉瘤中起癌基因作用。机制上，发现HCP5被转录因子SP1激活。最后，进行了挽救试验以证明SP1/HCP5轴在骨肉瘤中的功能。总之，我们证实SP1诱导的长链非编码RNA HCP5上调促进了骨肉瘤的发展。
