beta-Carotene 15,15 '-oxygenase inhibits cancer cell stemness and metastasis by regulating differentiation-related miRNAs in human neuroblastoma
- 주제(키워드) beta-Carotene 15 , 15 '-oxygenase , Neuroblastoma , Cancer stem cells , Metastasis , miRNA
- 주제(기타) Biochemistry & Molecular Biology; Nutrition & Dietetics
- 설명문(일반) [Kim, Yoo Sun; Kim, Yuri] Ewha Womans Univ, Dept Nutr Sci & Food Management, 52 Ewhayeodae Gil, Seoul 03760, South Korea; [Gong, Xiaoming] Texas Tech Univ, Hlth Sci Ctr, Dept Pediat, Paul L Foster Sch Med, El Paso, TX USA; [Rubin, Lewis P.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA; [Choi, Sang-Woon] CHA Univ, Chaum Life Ctr, Seoul 06062, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 ELSEVIER SCIENCE INC
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000160186
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.jnutbio.2019.03.010
- PubMed https://pubmed.ncbi.nlm.nih.gov/31048207
초록/요약
Neuroblastoma (NB) is the most common pediatric malignancy and is considered to possess cancer stem cells (CSCs) properties which can drive tumor initiation and metastasis. beta-carotene 15,15'-oxygenase (BCO1) is the main enzyme that catalyzes the first step in vitamin A biosynthesis from pro-vitamin A carotenoids. Retinoids (vitamin A) play a critical role in NB differentiation. However, the biological functions of BCOI in NB remained to be elucidated. Here, we investigated the effects of BCO1 on NB CSCs with stably expressing BCO1 in NB cells. We show that BCO1 significantly suppressed self-renewal and markers of NB CSCs. Moreover, BCO1 inhibited the metastatic potential of NB cells and suppressed the enzymatic activity and expression of MMPs, as well as expression of HIF-1 alpha and its downstream targets. In vivo, BCO1 reduced the metastatic incidence and volumes of metastatic tumors and downregulated the expression of CSCs markers, MMPs, and HIF-1 alpha in tumor tissues of a mouse xenograft model. A possible mechanism underlying the anti-cancer activities of BCO1 is proposed based on miRNAs sequencing array data which suggests a role for BCO11 in regulating miRNAs associated with neuronal differentiation, cell-cell adhesion, and the Wnt signaling pathway. Thus, our results demonstrate new chemotherapeutic roles for BCO1 in malignant NB that mediate suppression of cancer sternness and metastasis. (C) 2019 Elsevier Inc. All rights reserved.
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