Yu Guangyang, Liu Gang, Yuan Dongtang, Dai Jian, Cui Yin, Tang Xiaoming
Department of Orthopaedics, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, People's Republic of China.
Department of Orthopaedics, Nanjing general hospital of Nanjing military command, Nanjing, Jiangsu 210002, People's Republic of China.
J Bone Oncol. 2018 Feb 13;11:51-55. doi: 10.1016/j.jbo.2018.02.002. eCollection 2018 Jun.
Increasing evidence has shown that long noncoding RNAs (lncRNAs) ANRIL may function as oncogenes in various types of malignancies. However, there is still a lack of knowledge concerning its role in osteosarcoma (OS). In this study, we aimed to investigate the influence of ANRIL on cell proliferation and invasion of OS and to determine its association with clinicopathological features of the patients.
The tumor specimens and the adjacent normal tissues were collected from 57 OS patients and the expression level of ANRIL was quantified by RT-qPCR. High expression of ANRIL was defined as a relative mRNA expression of > 1.5 fold (tumor/normal). Knockdown of ANRIL was performed in human OS cell lines to investigate its influence on cell proliferation, apoptosis and invasion. In addition, expression of downstream genes in the transfected cells were determined by Western blot.
The expression level of ANRIL was significantly increased in OS tissues than in the adjacent normal tissues. 33 patients were included in the high expression group and the other 24 patients were included in the normal expression group. ANRIL expression was significantly associated with tumor size (5.7 cm ± 2.4 cm vs. 4.3 cm ± 1.7 cm, p = 0.02) and the 5-year survival rate (51.5% vs. 79.1%, p = 0.03). Knockdown of ANRIL could significantly induce cell apoptosis and inhibit cell proliferation and invasion. Moreover, knockdown of ANRIL could significantly decrease the expression level of phosphorylated PI3K and AKT in OS cells.
Upregulated expression of ANRIL is associated with the tumor development and prognosis of OS. ANRIL may regulate the function of OS cells through the AKT pathway.
越来越多的证据表明,长链非编码RNA(lncRNA)ANRIL在多种恶性肿瘤中可能发挥癌基因的作用。然而,关于其在骨肉瘤(OS)中的作用仍缺乏了解。在本研究中,我们旨在探讨ANRIL对OS细胞增殖和侵袭的影响,并确定其与患者临床病理特征的关系。
收集57例OS患者的肿瘤标本及癌旁正常组织,采用RT-qPCR定量检测ANRIL的表达水平。ANRIL高表达定义为相对mRNA表达>1.5倍(肿瘤/正常)。在人OS细胞系中敲低ANRIL,以研究其对细胞增殖、凋亡和侵袭的影响。此外,通过蛋白质免疫印迹法检测转染细胞中下游基因的表达。
OS组织中ANRIL的表达水平明显高于癌旁正常组织。33例患者纳入高表达组,另外24例患者纳入正常表达组。ANRIL表达与肿瘤大小(5.7 cm±2.4 cm vs. 4.3 cm±1.7 cm,p = 0.02)和5年生存率(51.5% vs. 79.1%,p = 0.03)显著相关。敲低ANRIL可显著诱导细胞凋亡,抑制细胞增殖和侵袭。此外,敲低ANRIL可显著降低OS细胞中磷酸化PI3K和AKT的表达水平。
ANRIL表达上调与OS的肿瘤发生发展及预后相关。ANRIL可能通过AKT通路调节OS细胞的功能。