Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway
Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway
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长链非编码RNA ANRIL在膀胱癌中表达上调，并通过内在途径调节膀胱癌细胞的增殖和凋亡。
DOI：
10.1016/j.bbrc.2015.10.002
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发表时间：
2015-11-13
影响因子：
3.1
通讯作者：
Xing, Yifei
中科院分区：
文献类型：
--
作者：
Zhu, Hongxue;Li, Xuechao;Xing, Yifei
INK4 基因座中的反义非编码 RNA (ANRIL) 是长非编码 RNA 的成员，据报道在多种人类癌症中失调。然而，ANRIL 在膀胱癌中的作用仍不清楚。本研究旨在调查 ANRIL 是否以及如何参与膀胱癌。我们的结果显示，与相应的邻近非肿瘤组织相比，膀胱癌组织中 ANRIL 上调。为了探索具体机制，通过小干扰RNA或短发夹RNA转染人膀胱癌T24和EJ细胞来沉默ANRIL。 ANRIL 的敲低抑制了细胞增殖并增加了细胞凋亡，同时 Bcl-2 的表达降低，Bax、细胞质细胞色素 c 和 Smac 以及裂解的 caspase-9、caspase-3 和 PARP 的表达增加。然而，没有观察到裂解的 caspase-8 水平的变化。此外，体内实验证实敲低ANRIL可抑制裸鼠EJ细胞的致瘤能力。同时，根据体外研究，敲低ANRIL会抑制Bcl-2的表达，上调Bax和cleaved caspase-9的表达，但不影响cleaved caspase-8的水平。总之，我们首次报道ANRIL可能作为膀胱癌的癌基因，并通过内在凋亡途径调节膀胱癌细胞的增殖和凋亡。 (C) 2015 Elsevier Inc. 保留所有权利。
Antisense non-coding RNA in the INK4 locus (ANRIL) is a member of long non-coding RNAs and has been reported to be dysregulated in several human cancers. However, the role of ANRIL in bladder cancer remains unclear. This present study aimed to investigate whether and how ANRIL involved in bladder cancer. Our results showed up-regulation of ANRIL in bladder cancer tissues versus the corresponding adjacent non-tumor tissues. To explore the specific mechanisms, ANRIL was silenced by small interfering RNA or short hairpin RNA transfection in human bladder cancer T24 and EJ cells. Knockdown of ANRIL repressed cell proliferation and increased cell apoptosis, along with decreased expression of Bcl-2 and increased expressions of Bax, cytoplasmic cytochrome c and Smac and cleaved caspase-9, caspase-3 and PARP. However, no change of cleaved caspase-8 level was observed. Furthermore, in vivo experiment confirmed that knockdown of ANRIL inhibited tumorigenic ability of EJ cells in nude mice. Meanwhile, in accordance with in vitro study, knockdown of ANRIL inhibited expression of Bcl-2 and up-regulated expressions of Bax and cleaved caspase-9, but did not affect cleaved caspase-8 level. In conclusion, we first report that ANRIL possibly serves as an oncogene in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic apoptosis pathway. (C) 2015 Elsevier Inc. All rights reserved.