SLCO4A1-AS1 promotes colorectal tumourigenesis by regulating Cdk2/c-Myc signalling.
SLCO4A1-AS1 promotes colorectal tumourigenesis by regulating Cdk2/c-Myc signalling.
复制标题
SLCO4A1-AS1通过调节Cdk2/c-Myc信号传导促进结直肠肿瘤的发生。
DOI：
10.1186/s12929-022-00789-z
复制
发表时间：
2022-01-17
影响因子：
11
通讯作者：
Huang Z
中科院分区：
文献类型：
--
作者：
Zhang J;Cui K;Huang L;Yang F;Sun S;Bian Z;Wang X;Li C;Yin Y;Huang S;Zhou L;Fei B;Huang Z
研究发现 SLCO4A1-AS1 在多种癌症类型中表达上调，包括结直肠癌 (CRC)。然而，SLCO4A1-AS1 在 CRC 中的详细作用仍有待阐明。因此，我们研究了SLCO4A1-AS1在结直肠肿瘤发生中的功能、机制和临床意义。我们使用 qRT-PCR 测量了 CRC 组织中 SLCO4A1-AS1 的表达，并确定其与患者预后的相关性。使用启动子甲基化分析来评估 SLCO4A1-AS1 的甲基化状态。使用功能获得和丧失测定来评估 SLCO4A1-AS1 对体外和体内 CRC 生长的影响。通过 RNA Pull-down、RNA 免疫沉淀、RNA-seq、荧光素酶报告基因和免疫组织化学分析来鉴定 SLCO4A1-AS1 在 CRC 中的分子机制。根据多个 CRC 队列，SLCO4A1-AS1 在 CRC 组织中经常上调，并且与不良预后相关。 CRC 中 SLCO4A1-AS1 的异常过度表达部分归因于其启动子的 DNA 低甲基化。异位SLCO4A1-AS1表达促进CRC细胞生长，而SLCO4A1-AS1敲低则抑制体外和体内CRC增殖。机理研究表明SLCO4A1-AS1作为分子支架增强Hsp90和Cdk2之间的相互作用，促进Cdk2的蛋白质稳定性。 SLCO4A1-AS1 诱导的 Cdk2 水平增加通过促进 c-Myc Ser62 磷酸化来激活 c-Myc 信号通路，从而导致肿瘤生长增加。我们的数据表明，SLCO4A1-AS1 通过调节 Hsp90/Cdk2/c-Myc 轴在 CRC 中充当癌基因，支持 SLCO4A1-AS1 作为 CRC 的潜在治疗靶点和预后因素。在线版本包含可在 10.1186/s12929-022-00789-z 获取的补充材料。
SLCO4A1-AS1 was found to be upregulated in several cancer types, including colorectal cancer (CRC). However, the detailed roles of SLCO4A1-AS1 in CRC remain to be elucidated. Therefore, we investigated the functions, mechanism, and clinical significance of SLCO4A1-AS1 in colorectal tumourigenesis. We measured the expression of SLCO4A1-AS1 in CRC tissues using qRT-PCR and determined its correlation with patient prognosis. Promoter methylation analyses were used to assess the methylation status of SLCO4A1-AS1. Gain- and loss-of-function assays were used to evaluate the effects of SLCO4A1-AS1 on CRC growth in vitro and in vivo. RNA pull-down, RNA immunoprecipitation, RNA-seq, luciferase reporter and immunohistochemistry assays were performed to identify the molecular mechanism of SLCO4A1-AS1 in CRC. SLCO4A1-AS1 was frequently upregulated in CRC tissues based on multiple CRC cohorts and was associated with poor prognoses. Aberrant overexpression of SLCO4A1-AS1 in CRC is partly attributed to the DNA hypomethylation of its promoter. Ectopic SLCO4A1-AS1 expression promoted CRC cell growth, whereas SLCO4A1-AS1 knockdown repressed CRC proliferation both in vitro and in vivo. Mechanistic investigations revealed that SLCO4A1-AS1 functions as a molecular scaffold to strengthen the interaction between Hsp90 and Cdk2, promoting the protein stability of Cdk2. The SLCO4A1-AS1-induced increase in Cdk2 levels activates the c-Myc signalling pathway by promoting the phosphorylation of c-Myc at Ser62, resulting in increased tumour growth. Our data demonstrate that SLCO4A1-AS1 acts as an oncogene in CRC by regulating the Hsp90/Cdk2/c-Myc axis, supporting SLCO4A1-AS1 as a potential therapeutic target and prognostic factor for CRC. The online version contains supplementary material available at 10.1186/s12929-022-00789-z.
登录
查看更多内容
影响因子：
4.6
作者：
Bian Z;Jin L;Zhang J;Yin Y;Quan C;Hu Y;Feng Y;Liu H;Fei B;Mao Y;Zhou L;Qi X;Huang S;Hua D;Xing C;Huang Z
通讯作者：
Huang Z
HDAC2通过下调结直肠癌中的长非编码RNA H19抑制EMT介导的癌症转移
DOI：
10.1186/s13046-020-01783-9
发表时间：
2020-12-02
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Hu XT;Xing W;Zhao RS;Tan Y;Wu XF;Ao LQ;Li Z;Yao MW;Yuan M;Guo W;Li SZ;Yu J;Ao X;Xu X
通讯作者：
Xu X
影响因子：
37.3
作者：
Augoff K;McCue B;Plow EF;Sossey-Alaoui K
通讯作者：
Sossey-Alaoui K
DOI：
10.1038/s41374-021-00577-7
发表时间：
2021-07
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
Wu K;Xu T;Song X;Shen J;Zheng S;Zhang L;Tao G;Jiang B
通讯作者：
Jiang B
DOI：
10.1007/978-1-4939-2425-7_25
发表时间：
2015-01-01
期刊：
PROTEIN-PROTEIN INTERACTIONS: METHODS AND APPLICATIONS, 2ND EDITION
影响因子：
--
作者：
Takahashi, Yoshinori
通讯作者：
Takahashi, Yoshinori