Kiang Karrie Mei-Yee, Zhang Xiao-Qin, Zhang Grace Pingde, Li Ning, Cheng Stephen Yin, Poon Ming-Wai, Pu Jenny Kan-Suen, Lui Wai-Man, Leung Gilberto Ka-Kit
Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, Hong Kong.
Target Oncol. 2017 Jun;12(3):353-363. doi: 10.1007/s11523-017-0488-3.
The long non-coding RNA CRNDE has emerged as an important regulator in carcinogenesis and cancer progression. While CRNDE has previously been found to be the most highly upregulated lncRNA in glioma, detailed information on its roles in regulating cancer cell growth remains limited.
In the present study, we aimed at exploring the functional roles and underlying mechanisms of CRNDE in glioma.
We applied microarray data analysis to determine the prognostic significance of CRNDE in glioma patients and its correlation with epidermal growth factor receptor (EGFR) activation. EGFR inhibition was used to confirm the role of EGFR in regulating CRNDE expression. Functional studies were performed upon CRNDE silencing to explore its role in gliomagenesis.
We confirm that CRNDE acts as an oncogene that is highly up-regulated in glioma, and high CRNDE expression correlates with poor prognosis in glioma patients. We further demonstrate that the expression of CRNDE correlates with EGFR activation. EGF and EGFR tyrosine kinase inhibitor (TKI) enhance and block the up-regulation of CRNDE expression, respectively, suggesting that EGFR signaling may positively regulate CRNDE expression. Functional assays show that CRNDE depletion inhibits glioma cell growth both in vitro and in vivo, and is associated with induced cellular apoptosis with decreased Bcl2/Bax ratio.
Our findings suggest that the aberrant expression of CRNDE may be mediated by activated EGFR signaling and play significant roles in gliomagenesis.
长链非编码RNA CRNDE已成为肿瘤发生和癌症进展中的重要调节因子。虽然此前已发现CRNDE是胶质瘤中上调程度最高的长链非编码RNA,但其在调节癌细胞生长中的作用的详细信息仍然有限。
在本研究中,我们旨在探讨CRNDE在胶质瘤中的功能作用及潜在机制。
我们应用微阵列数据分析来确定CRNDE在胶质瘤患者中的预后意义及其与表皮生长因子受体(EGFR)激活的相关性。使用EGFR抑制来证实EGFR在调节CRNDE表达中的作用。对CRNDE沉默进行功能研究以探索其在胶质瘤发生中的作用。
我们证实CRNDE作为一种癌基因在胶质瘤中高度上调,且CRNDE高表达与胶质瘤患者的不良预后相关。我们进一步证明CRNDE的表达与EGFR激活相关。表皮生长因子(EGF)和EGFR酪氨酸激酶抑制剂(TKI)分别增强和阻断CRNDE表达的上调,提示EGFR信号可能正向调节CRNDE表达。功能分析表明,CRNDE缺失在体外和体内均抑制胶质瘤细胞生长,并与诱导细胞凋亡及降低的Bcl2/Bax比值相关。
我们的研究结果表明,CRNDE的异常表达可能由激活的EGFR信号介导,并在胶质瘤发生中起重要作用。