LncRNA ANCR promotes glioma cells invasion, migration, proliferation and inhibits apoptosis via interacting with EZH2 and repressing PTEN expression
LncRNA ANCR promotes glioma cells invasion, migration, proliferation and inhibits apoptosis via interacting with EZH2 and repressing PTEN expression
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DOI：
10.1038/s41417-020-00263-8
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发表时间：
2020-12-08
影响因子：
6.4
通讯作者：
Ji, Ying
中科院分区：
文献类型：
--
作者：
Cheng, Chuandong;Dong, Yongfei;Ji, Ying
近年来，长链非编码RNA（lncRNA）在人类疾病中的作用已被证实，我们的目的是探讨lncRNA抗分化非编码RNA（ANCR）在胶质瘤中的作用。用RT-PCR或Western blot检测胶质瘤组织和细胞中lncRNA ANCR、zeste增强子同源物2（EZH 2）和磷酸酶和张力蛋白同源物（PTEN）的表达。采用Pearson检验分析ANCR、EZH 2和PTEN在胶质瘤组织中的表达。进行细胞凋亡、transwell侵袭、迁移、集落形成和增殖测定以评估lncRNA ANCR缺失、EZH 2减少或PTEN升高对胶质瘤细胞的细胞生物学的影响。通过RIP、RNA pull-down和染色质免疫沉淀试验证实ANCR与EZH 2、EZH 2与PTEN之间的关系。我们的研究结果表明，ANCR和EZH 2在胶质瘤组织和细胞系中表达上调，而PTEN表达下调。ANCR表达与EZH 2表达呈正相关，而PTEN表达与ANCR/EZH 2表达呈负相关。抑制ANCR、降低EZH 2或升高PTEN均能降低胶质瘤细胞的侵袭、迁移和增殖能力，促进胶质瘤细胞凋亡。PTEN过表达或EZH 2抑制可逆转ANCR上调对胶质瘤细胞生长和转移的促进作用。在机制上，PTEN在ANCR敲低的胶质瘤细胞中上调。在胶质瘤细胞中EZH 2与ANCR相互作用。综上所述，我们发现抑制ANCR可以通过与EZH 2相互作用，调节PTEN的表达，抑制胶质瘤细胞的侵袭、迁移、增殖，促进胶质瘤细胞凋亡，为胶质瘤患者提供了一个有效的治疗靶点。
Recently, the role of long noncoding RNA (lncRNA) has been identified in human diseases, and we aim to explore the role of lncRNA antidifferentiation noncoding RNA (ANCR) in glioma. Expression of lncRNA ANCR, enhancer of zeste homolog 2 (EZH2), and phosphatase and tensin homolog (PTEN) in glioma tissues and cells was determined by RT-PCR or western blot assay. The correlation between expression of ANCR, EZH2, and PTEN in glioma tissues was analyzed using Pearson test. The apoptosis, transwell invasion, migration, colony formation, and proliferation assays were conducted to evaluate the influences of lncRNA ANCR depletion, EZH2 reduction, or PTEN elevation on the cell biology of glioma cells. The relationships between ANCR and EZH2, and between EZH2 and PTEN were confirmed through RIP, RNA pull-down, and chromatin immunoprecipitation assays. Our results indicated that ANCR and EZH2 were upregulated and PTEN was downregulated in glioma tissues and cell lines. ANCR expression was positively related to EZH2 expression, while PTEN expression was negatively related to ANCR/EZH2 expression. Inhibited ANCR, reduced EZH2, or elevated PTEN could reduce the ability of invasion, migration, and proliferation, and promote apoptosis of glioma cells. PTEN overexpression or EZH2 inhibition reversed the promotive role of ANCR upregulation in glioma cell growth and metastasis. Mechanistically, PTEN was upregulated in ANCR knockdown glioma cells. EZH2 interacted with ANCR in glioma cells. In conclusion, we have found that restrained ANCR could repress invasion, migration, and proliferation, as well as promote apoptosis of glioma cells through interacting with EZH2 and regulating the expression of PTEN, offering an effective therapeutic target for patients with glioma.