Zhang Xuedong, Zhang Yakui, Mao Yong, Ma Xinlong
Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin.
Department of Orthopedics, Beijing Luhe Hospital, Capital Medical University, Beijing, People's Republic of China.
Onco Targets Ther. 2018 Jan 31;11:629-638. doi: 10.2147/OTT.S152063. eCollection 2018.
Osteosarcoma is a malignant primary bone cancer and is lethal to children and adolescents. Recently, the dysregulation of long noncoding RNAs (lncRNAs) has been shown in various types of cancers.
The present study aimed to examine the role of the lncRNA prostate cancer-associated transcript 1 (PCAT1) in osteosarcoma progression.
The expression levels of relevant genes in clinical samples and cell lines were determined by quantitative real-time polymerase chain reaction. Cell proliferation, invasion and migration were examined by CCK-8 assay, transwell invasion and migration assay, respectively. Cell apoptosis and cell cycle were detected by flow cytometry. Protein levels were detected by Western blot.
Our results showed that PCAT1 was upregulated in osteosarcoma tissues when compared to normal bone tissues. PCAT1 was also upregulated in osteosarcoma cell lines when compared to normal bone cell line. The upregulation of PCAT1 was significantly associated with advanced clinical stage, tumor metastasis and shorter overall survival in patients with osteosarcoma. In vitro studies showed that overexpression of PCAT1 in MG-63 cells enhanced cell proliferation, cell invasion and migration and epithelial-to-mesenchymal transition (EMT); decreased cell apoptotic rate; and also caused an increase in cell population at S phase with a decrease in cell population at G/G phase. Knockdown of PCAT1 in U2OS cells suppressed cell proliferation, cell invasion and migration, and EMT; increased cell apoptotic rate; and caused an increase in the cell population at G/G phase with a decrease in cell population at S phase.
Taken together, our results suggest the oncogenic role of PCAT1 in osteosarcoma progression.
骨肉瘤是一种原发性恶性骨癌,对儿童和青少年具有致命性。最近,长链非编码RNA(lncRNA)的失调已在多种类型的癌症中得到证实。
本研究旨在探讨lncRNA前列腺癌相关转录本1(PCAT1)在骨肉瘤进展中的作用。
通过定量实时聚合酶链反应测定临床样本和细胞系中相关基因的表达水平。分别采用CCK-8法、Transwell侵袭和迁移实验检测细胞增殖、侵袭和迁移能力。通过流式细胞术检测细胞凋亡和细胞周期。采用蛋白质免疫印迹法检测蛋白质水平。
我们的结果显示,与正常骨组织相比,PCAT1在骨肉瘤组织中上调。与正常骨细胞系相比,PCAT1在骨肉瘤细胞系中也上调。PCAT1的上调与骨肉瘤患者的临床晚期、肿瘤转移及较短的总生存期显著相关。体外研究表明,MG-63细胞中PCAT1的过表达增强了细胞增殖、侵袭、迁移及上皮-间质转化(EMT);降低了细胞凋亡率;还导致S期细胞数量增加,G/G期细胞数量减少。U2OS细胞中PCAT1的敲低抑制了细胞增殖、侵袭、迁移及EMT;增加了细胞凋亡率;导致G/G期细胞数量增加,S期细胞数量减少。
综上所述,我们的结果提示PCAT1在骨肉瘤进展中具有致癌作用。