Oncogenic lncRNA ZNF561-AS1 is essential for colorectal cancer proliferation and survival through regulation of miR-26a-3p/miR-128-5p-SRSF6 axis.
Oncogenic lncRNA ZNF561-AS1 is essential for colorectal cancer proliferation and survival through regulation of miR-26a-3p/miR-128-5p-SRSF6 axis.
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DOI：
10.1186/s13046-021-01882-1
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发表时间：
2021-02-23
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Si Z;Yu L;Jing H;Wu L;Wang X
据报道，长非编码 RNA (lncRNA) 会影响结直肠癌 (CRC) 的进展。目前，lncRNA ZNF561 反义 RNA 1 (ZNF561-AS1) 在 CRC 中的功能尚不清楚。通过 TCGA 数据库分析、蛋白质印迹以及实时 PCR 评估 CRC 患者样本和 CRC 细胞系中的 ZNF561-AS1 和 SRSF6 表达。还在 ZNF561-AS1 耗尽或过度表达时检查了 CRC 细胞中的 SRSF6 表达。通过双荧光素酶报告基因测定以及 RNA 结合蛋白免疫沉淀 (RIP) 测定检查 miR-26a-3p、miR-128-5p、ZNF561-AS1 和 SRSF6 之间的相互作用。进行小干扰RNA（siRNA）介导的敲低实验来评估ZNF561-AS1和SRSF6在CRC细胞的增殖活性和凋亡率中的作用。采用小鼠异种移植模型来评估 ZNF561-AS1 敲低和 SRSF6 拯救后的肿瘤生长。我们发现 ZNF561-AS1 和 SRSF6 在 CRC 患者组织中表达上调。 ZNF561-AS1 的表达在接受治疗的 CRC 患者的组织中降低，但在复发患者的 CRC 组织中表达上调。 ZNF561-AS1 缺失和过表达分别抑制和增强 SRSF6 表达。从机制上讲，ZNF561-AS1 通过海绵 miR-26a-3p 和 miR-128-5p 调节 SRSF6 表达。 ZNF561-AS1-miR-26a-3p/miR-128-5p-SRSF6 轴是 CRC 增殖和存活所必需的。 ZNF561-AS1 敲除抑制 CRC 细胞增殖并引发细胞凋亡。 ZNF561-AS1 缺失抑制了裸鼠异种移植模型中肿瘤的生长。对 SRSF6 耗尽也进行了类似的观察。 SRSF6 过表达逆转了 ZNF561-AS1 体内和体外的抑制活性。总之，我们发现 ZNF561-AS1 通过 miR-26a-3p/miR-128-5p-SRSF6 轴促进 CRC 进展。这项研究揭示了 ZNF561-AS1 在 CRC 中的作用的新视角。在线版本包含可在 10.1186/s13046-021-01882-1 获取的补充材料。
Long non-coding RNAs (lncRNA) are reported to influence colorectal cancer (CRC) progression. Currently, the functions of the lncRNA ZNF561 antisense RNA 1 (ZNF561-AS1) in CRC are unknown. ZNF561-AS1 and SRSF6 expression in CRC patient samples and CRC cell lines was evaluated through TCGA database analysis, western blot along with real-time PCR. SRSF6 expression in CRC cells was also examined upon ZNF561-AS1 depletion or overexpression. Interaction between miR-26a-3p, miR-128-5p, ZNF561-AS1, and SRSF6 was examined by dual luciferase reporter assay, as well as RNA binding protein immunoprecipitation (RIP) assay. Small interfering RNA (siRNA) mediated knockdown experiments were performed to assess the role of ZNF561-AS1 and SRSF6 in the proliferative actives and apoptosis rate of CRC cells. A mouse xenograft model was employed to assess tumor growth upon ZNF561-AS1 knockdown and SRSF6 rescue. We find that ZNF561-AS1 and SRSF6 were upregulated in CRC patient tissues. ZNF561-AS1 expression was reduced in tissues from treated CRC patients but upregulated in CRC tissues from relapsed patients. SRSF6 expression was suppressed and enhanced by ZNF561-AS1 depletion and overexpression, respectively. Mechanistically, ZNF561-AS1 regulated SRSF6 expression by sponging miR-26a-3p and miR-128-5p. ZNF561-AS1-miR-26a-3p/miR-128-5p-SRSF6 axis was required for CRC proliferation and survival. ZNF561-AS1 knockdown suppressed CRC cell proliferation and triggered apoptosis. ZNF561-AS1 depletion suppressed the growth of tumors in a model of a nude mouse xenograft. Similar observations were made upon SRSF6 depletion. SRSF6 overexpression reversed the inhibitory activities of ZNF561-AS1 in vivo, as well as in vitro. In summary, we find that ZNF561-AS1 promotes CRC progression via the miR-26a-3p/miR-128-5p-SRSF6 axis. This study reveals new perspectives into the role of ZNF561-AS1 in CRC. The online version contains supplementary material available at 10.1186/s13046-021-01882-1.
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影响因子：
12.3
作者：
Rigoutsos I;Lee SK;Nam SY;Anfossi S;Pasculli B;Pichler M;Jing Y;Rodriguez-Aguayo C;Telonis AG;Rossi S;Ivan C;Catela Ivkovic T;Fabris L;Clark PM;Ling H;Shimizu M;Redis RS;Shah MY;Zhang X;Okugawa Y;Jung EJ;Tsirigos A;Huang L;Ferdin J;Gafà R;Spizzo R;Nicoloso MS;Paranjape AN;Shariati M;Tiron A;Yeh JJ;Teruel-Montoya R;Xiao L;Melo SA;Menter D;Jiang ZQ;Flores ER;Negrini M;Goel A;Bar-Eli M;Mani SA;Liu CG;Lopez-Berestein G;Berindan-Neagoe I;Esteller M;Kopetz S;Lanza G;Calin GA
通讯作者：
Calin GA
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影响因子：
28.5
作者：
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影响因子：
16.6
作者：
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影响因子：
28.2
作者：
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通讯作者：
Pandolfi PP
影响因子：
7.3
作者：
Cohen-Eliav, Michal;Golan-Gerstl, Regina;Karni, Rotem
通讯作者：
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