Long noncoding RNA ZEB1-AS1 epigenetically regulates the expressions of ZEB1 and downstream molecules in prostate cancer.
Long noncoding RNA ZEB1-AS1 epigenetically regulates the expressions of ZEB1 and downstream molecules in prostate cancer.
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长非编码RNA ZEB1-AS1表观遗传调节前列腺癌中ZEB1及下游分子的表达
DOI：
10.1186/s12943-017-0711-y
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发表时间：
2017-08-23
期刊：
影响因子：
37.3
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Su W;Xu M;Chen X;Chen N;Gong J;Nie L;Li L;Li X;Zhang M;Zhou Q
背景研究表明长链非编码RNA（longnoncodingRNAs，lncRNAs）在肿瘤的发生、发展过程中起重要作用。lncRNAZEB 1反义1（ZEB 1-AS 1）来源于ZEB 1的启动子区，目前对ZEB 1的表达、作用及机制尚不清楚。利用RNA干扰降低ZEB 1-AS 1的表达。使用腺病毒表达载体来增加ZEB 1-AS 1的表达。CHIP和RIP用于检测ZEB 1-AS 1调控ZEB 1的表观遗传机制。结果在本研究中，我们发现在前列腺癌细胞中，RNA干扰介导的ZEB 1-AS 1下调可诱导显著的ZEB 1抑制，而人工过表达ZEB 1-AS 1则可挽救ZEB 1的表达，这意味着ZEB 1-AS 1促进ZEB 1的表达。此外，ZEB 1-AS 1间接抑制ZEB 1的已知靶点miR 200 c，并上调miR 200 c的靶点BMI 1。在机制上，ZEB 1-AS 1结合并募集组蛋白甲基转移酶MLL 1至ZEB 1的启动子区，诱导其中的H3 K4 me 3修饰，并激活ZEB 1转录。在生物学上，ZEB 1-AS 1促进前列腺癌细胞的增殖和迁移。ConclusionsCollectively，ZEB 1-AS 1功能作为一个癌基因在前列腺癌通过表观遗传激活ZEB 1和间接调节下游分子的ZEB 1。
BackgroundEmerging studies show that long noncoding RNAs (lncRNAs) play important roles in carcinogenesis and cancer progression. The lncRNA ZEB1 antisense 1 (ZEB1-AS1) derives from the promoter region of ZEB1 and we still know little about its expressions, roles and mechanisms.MethodsRACE was used to obtain the sequence of ZEB1-AS1. RNA interference was used to decrease ZEB1-AS1 expression. Adenovirus expression vector was used to increase ZEB1-AS1 expression. CHIP and RIP were used to detect the epigenetic mechanisms by which ZEB1-AS1 regulated ZEB1. CCK8 assay, wound healing assay and transwell assay were used to measure proliferation and migration of prostate cancer cells.ResultsIn this study, in prostate cancer cells, we found that RNAi-mediated downregulation of ZEB1-AS1 induced significant ZEB1 inhibition while artificial overexpression of ZEB1-AS1 rescued ZEB1 expression, which means that ZEB1-AS1 promotes ZEB1 expression. Also, ZEB1-AS1 indirectly inhibited miR200c, the well-known target of ZEB1, and upregulated miR200c’s target BMI1. Mechanistically, ZEB1-AS1 bound and recruited histone methyltransferase MLL1 to the promoter region of ZEB1, induced H3K4me3 modification therein, and activated ZEB1 transcription. Biologically, ZEB1-AS1 promoted proliferation and migration of prostate cancer cells.ConclusionsCollectively, ZEB1-AS1 functions as an oncogene in prostate cancer via epigenetically activating ZEB1 and indirectly regulating downstream molecules of ZEB1.
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