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CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression

Hepatoblastoma (HB) is a malignant embryonal tumor of the liver that consists of heterogenous populations of stem/progenitor cells. Although circular RNAs (circRNAs) play an essential role in tumor development, the effects of circRNA on the proliferation of HB cells, especially cancer stem cells (CS...

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Autores principales: Chen, Luping, Shi, Juanyi, Wu, Yaohao, Qiu, Ronglin, Zeng, Lexiang, Lou, Lei, Su, Jianhang, Liao, Minyi, Deng, Xiaogeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732296/
https://www.ncbi.nlm.nih.gov/pubmed/33052880
http://dx.doi.org/10.18632/aging.103748
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author Chen, Luping
Shi, Juanyi
Wu, Yaohao
Qiu, Ronglin
Zeng, Lexiang
Lou, Lei
Su, Jianhang
Liao, Minyi
Deng, Xiaogeng
author_facet Chen, Luping
Shi, Juanyi
Wu, Yaohao
Qiu, Ronglin
Zeng, Lexiang
Lou, Lei
Su, Jianhang
Liao, Minyi
Deng, Xiaogeng
author_sort Chen, Luping
collection PubMed
description Hepatoblastoma (HB) is a malignant embryonal tumor of the liver that consists of heterogenous populations of stem/progenitor cells. Although circular RNAs (circRNAs) play an essential role in tumor development, the effects of circRNA on the proliferation of HB cells, especially cancer stem cells (CSCs), remain unclear. We found that the circRNA, CDR1as, was highly expressed in CSC-enriched populations of HB cell lines. Results from flow cytometric and sphere-forming assays revealed that CDR1as knockdown in HB cell lines decreased the proportion of stem cells. The Cell Counting Kit-8 (CCK-8) assay, colony formation experiments, and EdU assay revealed that CDR1as knockdown in HB cell lines decreased cell growth and the colony-forming abilities. Biotin-coupled probe pull-down assays and biotin-coupled microRNA capture were conducted to evaluate the interaction between CDR1as and miR-7-5p. Dual-luciferase reporter assays demonstrated that Kruppel-like factor 4 (KLF4), expression of which is highly correlated with cancer stemness, was a target of miR-7-5p. Overall, the knockdown of CDR1as significantly inhibited the proliferation and stemness of HB cells by reducing the sponge activity on miR-7-5p and subsequently suppressing the interaction between miR-7-5p and KLF4. Results from this study suggest that CDR1as is an oncogene that effects the proliferation and stemness of HBs.
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spelling pubmed-77322962020-12-18 CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression Chen, Luping Shi, Juanyi Wu, Yaohao Qiu, Ronglin Zeng, Lexiang Lou, Lei Su, Jianhang Liao, Minyi Deng, Xiaogeng Aging (Albany NY) Research Paper Hepatoblastoma (HB) is a malignant embryonal tumor of the liver that consists of heterogenous populations of stem/progenitor cells. Although circular RNAs (circRNAs) play an essential role in tumor development, the effects of circRNA on the proliferation of HB cells, especially cancer stem cells (CSCs), remain unclear. We found that the circRNA, CDR1as, was highly expressed in CSC-enriched populations of HB cell lines. Results from flow cytometric and sphere-forming assays revealed that CDR1as knockdown in HB cell lines decreased the proportion of stem cells. The Cell Counting Kit-8 (CCK-8) assay, colony formation experiments, and EdU assay revealed that CDR1as knockdown in HB cell lines decreased cell growth and the colony-forming abilities. Biotin-coupled probe pull-down assays and biotin-coupled microRNA capture were conducted to evaluate the interaction between CDR1as and miR-7-5p. Dual-luciferase reporter assays demonstrated that Kruppel-like factor 4 (KLF4), expression of which is highly correlated with cancer stemness, was a target of miR-7-5p. Overall, the knockdown of CDR1as significantly inhibited the proliferation and stemness of HB cells by reducing the sponge activity on miR-7-5p and subsequently suppressing the interaction between miR-7-5p and KLF4. Results from this study suggest that CDR1as is an oncogene that effects the proliferation and stemness of HBs. Impact Journals 2020-10-14 /pmc/articles/PMC7732296/ /pubmed/33052880 http://dx.doi.org/10.18632/aging.103748 Text en Copyright: © 2020 Chen et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Chen, Luping
Shi, Juanyi
Wu, Yaohao
Qiu, Ronglin
Zeng, Lexiang
Lou, Lei
Su, Jianhang
Liao, Minyi
Deng, Xiaogeng
CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression
title CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression
title_full CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression
title_fullStr CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression
title_full_unstemmed CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression
title_short CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression
title_sort circrna cdr1as promotes hepatoblastoma proliferation and stemness by acting as a mir-7-5p sponge to upregulate klf4 expression
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732296/
https://www.ncbi.nlm.nih.gov/pubmed/33052880
http://dx.doi.org/10.18632/aging.103748
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