Cellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/β-catenin pathway in hepatocellular carcinoma.
Cellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/β-catenin pathway in hepatocellular carcinoma.
复制标题
细胞视黄醇结合蛋白-1 通过上调 WIF1 抑制肝细胞癌中的 Wnt/β-catenin 通路来抑制癌症干性
DOI：
10.1186/s12885-021-08967-2
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发表时间：
2021-11-14
期刊：
影响因子：
3.8
通讯作者：
Tang R
中科院分区：
文献类型：
--
作者：
Liu X;Shan W;Li T;Gao X;Kong F;You H;Kong D;Qiao S;Tang R
背景CRBP-1是维生素A的胞质伴侣，在许多癌症中被鉴定;然而，其在肝细胞癌（HCC）中的生物学作用需要进一步探索。本研究的目的是探讨CRBP-1在调节肝癌中的作用和机制，通过体外和体内生物学方法。方法采用免疫组化方法检测CRBP-1在肝癌组织和癌旁肝组织中的表达水平。在建立稳定的CRBP-1过表达HCC细胞系后，在体外和体内研究细胞生长和致瘤性。通过ELISA定量细胞内视黄酸。CRBP-1和WIF 1之间的关系进行了验证，通过使用双荧光素酶和ChIP analysis.ResultsThe低表达的CRBP-1被观察到在肝癌组织相比，正常肝组织，而高CRBP-1表达与临床病理特征和增加总生存率在肝癌患者。CRBP-1的过表达在体内外均显著抑制细胞生长和致瘤性。此外，CRBP-1的过表达抑制了HCC中肿瘤球的形成和癌干细胞相关基因的表达。CRBP-1通过抑制Wnt/β-catenin信号通路抑制肝癌细胞的干细胞性。CRBP-1通过与WIF 1启动子区域的物理相互作用，增加细胞内视黄酸的水平，从而激活RAR/RXR，导致WIF 1（Wnt/β-catenin信号通路的分泌拮抗剂）的转录表达。结论CRBP-1在HCC的发生和发展中起重要作用。其为HCC的诊断和治疗提供了新的独立的预后生物标志物和治疗靶点。
BackgroundCRBP-1, a cytosolic chaperone of vitamin A, is identified in a serious number of cancers; however, its biological role in hepatocellular carcinoma (HCC) needs to be further explored. The aim of our present study is to explore the roles and mechanisms of CRBP-1 in regulating liver cancer by using in vitro and in vivo biology approaches.MethodsThe expression level of CRBP-1 was detected using immunohistochemistry in HCC and matching adjacent non-tumorous liver tissues. Following established stable CRBP-1 overexpressed HCC cell lines, the cell growth and tumorigenicity were investigated both in vitro and in vivo. Intracellular retinoic acid was quantified by ELISA. The relationship between CRBP-1 and WIF1 was validated by using dual luciferase and ChIP analyses.ResultsThe low expression of CRBP-1 was observed in HCC tissues compared to the normal liver tissues, while high CRBP-1 expression correlated with clinicopathological characteristics and increased overall survival in HCC patients. Overexpression of CRBP-1 significantly inhibited cell growth and tumorigenicity both in vitro and in vivo. Moreover, overexpression of CRBP-1 suppressed tumorsphere formation and cancer stemness related genes expression in HCC. Mechanically, CRBP-1 inhibited Wnt/β-catenin signaling pathway to suppress cancer cell stemness of HCC. Furthermore, our results revealed that CRBP-1 could increase the intracellular levels of retinoic acid, which induced the activation of RARs/RXRs leading to the transcriptional expression of WIF1, a secreted antagonist of the Wnt/β-catenin signaling pathway, by physically interacting with the region on WIF1 promoter.ConclusionOur findings reveal that CRBP-1 is a crucial player in the initiation and progression of HCC, which provide a novel independent prognostic biomarker and therapeutic target for the diagnosis and treatment of HCC.
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影响因子：
3.8
作者：
Chen Y;Tian T;Mao MJ;Deng WY;Li H
通讯作者：
Li H
影响因子：
1.6
作者：
Matsui WH
通讯作者：
Matsui WH
影响因子：
6
作者：
Campos, Benito;Centner, Franz-Simon;Herold-Mende, Christel
通讯作者：
Herold-Mende, Christel
影响因子：
5.1
作者：
Hoegberg, P;Schmidt, CK;Håkansson, H
通讯作者：
Håkansson, H
影响因子：
56.9
作者：
He, TC;Sparks, AB;Kinzler, KW
通讯作者：
Kinzler, KW