Cellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/β-catenin pathway in hepatocellular carcinoma

Abstract Background CRBP-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...

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Autores principales:	Xiangye Liu, Wenhua Shan, Tingting Li, Xiaoge Gao, Fanyun Kong, Hongjuan You, Delong Kong, Shuxi Qiao, Renxian Tang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Cellular retinol binding protein-1 Hepatocellular carcinoma Cancer stemness Retinoic acid Wnt inhibitory factor 1 Wnt/β-catenin signaling pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a8e010a05b0c4c8aab6ce3172338d044
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spelling	oai:doaj.org-article:a8e010a05b0c4c8aab6ce3172338d0442021-11-14T12:30:23ZCellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/β-catenin pathway in hepatocellular carcinoma10.1186/s12885-021-08967-21471-2407https://doaj.org/article/a8e010a05b0c4c8aab6ce3172338d0442021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08967-2https://doaj.org/toc/1471-2407Abstract Background CRBP-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. Methods The 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. Results The 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. Conclusion Our 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.Xiangye LiuWenhua ShanTingting LiXiaoge GaoFanyun KongHongjuan YouDelong KongShuxi QiaoRenxian TangBMCarticleCellular retinol binding protein-1Hepatocellular carcinomaCancer stemnessRetinoic acidWnt inhibitory factor 1Wnt/β-catenin signaling pathwayNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cellular retinol binding protein-1 Hepatocellular carcinoma Cancer stemness Retinoic acid Wnt inhibitory factor 1 Wnt/β-catenin signaling pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Cellular retinol binding protein-1 Hepatocellular carcinoma Cancer stemness Retinoic acid Wnt inhibitory factor 1 Wnt/β-catenin signaling pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Xiangye Liu Wenhua Shan Tingting Li Xiaoge Gao Fanyun Kong Hongjuan You Delong Kong Shuxi Qiao Renxian Tang Cellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/β-catenin pathway in hepatocellular carcinoma
description	Abstract Background CRBP-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. Methods The 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. Results The 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. Conclusion Our 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.
format	article
author	Xiangye Liu Wenhua Shan Tingting Li Xiaoge Gao Fanyun Kong Hongjuan You Delong Kong Shuxi Qiao Renxian Tang
author_facet	Xiangye Liu Wenhua Shan Tingting Li Xiaoge Gao Fanyun Kong Hongjuan You Delong Kong Shuxi Qiao Renxian Tang
author_sort	Xiangye Liu
title	Cellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/β-catenin pathway in hepatocellular carcinoma
title_short	Cellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/β-catenin pathway in hepatocellular carcinoma
title_full	Cellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/β-catenin pathway in hepatocellular carcinoma
title_fullStr	Cellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/β-catenin pathway in hepatocellular carcinoma
title_full_unstemmed	Cellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/β-catenin pathway in hepatocellular carcinoma
title_sort	cellular retinol binding protein-1 inhibits cancer stemness via upregulating wif1 to suppress wnt/β-catenin pathway in hepatocellular carcinoma
publisher	BMC
publishDate	2021
url	https://doaj.org/article/a8e010a05b0c4c8aab6ce3172338d044
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Cellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/β-catenin pathway in hepatocellular carcinoma

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