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Suppression of metastasis through inhibition of chitinase 3-like 1 expression by miR-125a-3p-mediated up-regulation of USF1

Rationale: Chitinase 3-like 1 (Chi3L1) protein is up-regulated in various diseases including solid cancers. According to Genome-Wide Association Study (GWAS)/Online Mendelian Inheritance in Man (OMIM)/Differentially Expressed Gene (DEG) analyses, Chi3L1 is associated with 38 cancers, and more highly...

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Autores principales: Kim, Ki Cheon, Yun, Jaesuk, Son, Dong Ju, Kim, Ji Young, Jung, Jae-Kyung, Choi, Jeong Soon, Kim, Yu Ri, Song, Ju Kyung, Kim, Sun Young, Kang, Sin Kook, Shin, Dae Hwan, Roh, Yoon-Seok, Han, Sang-Bae, Hong, Jin Tae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134921/
https://www.ncbi.nlm.nih.gov/pubmed/30214629
http://dx.doi.org/10.7150/thno.26467
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author Kim, Ki Cheon
Yun, Jaesuk
Son, Dong Ju
Kim, Ji Young
Jung, Jae-Kyung
Choi, Jeong Soon
Kim, Yu Ri
Song, Ju Kyung
Kim, Sun Young
Kang, Sin Kook
Shin, Dae Hwan
Roh, Yoon-Seok
Han, Sang-Bae
Hong, Jin Tae
author_facet Kim, Ki Cheon
Yun, Jaesuk
Son, Dong Ju
Kim, Ji Young
Jung, Jae-Kyung
Choi, Jeong Soon
Kim, Yu Ri
Song, Ju Kyung
Kim, Sun Young
Kang, Sin Kook
Shin, Dae Hwan
Roh, Yoon-Seok
Han, Sang-Bae
Hong, Jin Tae
author_sort Kim, Ki Cheon
collection PubMed
description Rationale: Chitinase 3-like 1 (Chi3L1) protein is up-regulated in various diseases including solid cancers. According to Genome-Wide Association Study (GWAS)/Online Mendelian Inheritance in Man (OMIM)/Differentially Expressed Gene (DEG) analyses, Chi3L1 is associated with 38 cancers, and more highly associated with cancer compared to other oncogenes such as EGFR, TNFα, etc. However, the mechanisms and pathways by which Chi3L1 is associated with cancer are not clear. In current study, we investigated the role of Chi3L1 in lung metastasis. Methods: We performed the differentially expressed gene analysis to explore the genes which are associated with Chi3L1 using the web-based platform from Biomart. We investigated the metastases in lung tissues of C57BL/6 mice injected with B16F10 melanoma following treatment with Ad-shChi3L1. We also investigated the expression of USF1 and Chi3L1 in Chi3L1 KD mice lung tissues by Western blotting and IHC. We also analyzed lung cancer cells metastases induced by Chi3L1 using migration and cell proliferation assay in human lung cancer cell lines. The involvement of miR-125a-3p in Chi3L1 regulation was determined by miRNA qPCR and luciferase reporter assay. Results: We showed that melanoma metastasis in lung tissues was significantly reduced in Chi3L1 knock-down mice, accompanied by down-regulation of MMP-9, MMP-13, VEGF, and PCNA in Chi3L1 knock-down mice lung tissue, as well as in human lung cancer cell lines. We also found that USF1 was conversely expressed against Chi3L1. USF1 was increased by knock-down of Chi3L1 in mice lung tissues, as well as in human lung cancer cell lines. In addition, knock-down of USF1 increased Chi3L1 levels in addition to augmenting metastasis cell migration and proliferation in mice model, as well as in human cancer cell lines. Moreover, in human lung tumor tissues, the expression of Chi3L1 was increased but USF1 was decreased in a stage-dependent manner. Finally, Chi3L1 expression was strongly regulated by the indirect translational suppressing activity of USF1 through induction of miR-125a-3p, a target of Chi3L1. Conclusion: Metastases in mice lung tissues and human lung cancer cell lines were decreased by KD of Chi3L1. USF1 bound to the Chi3L1 promoter, however, Chi3L1 expression was decreased by USF1, despite USF1 enhancing the transcriptional activity of Chi3L1. We found that USF1 induced miR-125a-3p levels which suppressed Chi3L1 expression. Ultimately, our results suggest that lung metastasis is suppressed by knock-down of Chi3L1 through miR-125a-3p-mediated up-regulation of USF1.
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spelling pubmed-61349212018-09-13 Suppression of metastasis through inhibition of chitinase 3-like 1 expression by miR-125a-3p-mediated up-regulation of USF1 Kim, Ki Cheon Yun, Jaesuk Son, Dong Ju Kim, Ji Young Jung, Jae-Kyung Choi, Jeong Soon Kim, Yu Ri Song, Ju Kyung Kim, Sun Young Kang, Sin Kook Shin, Dae Hwan Roh, Yoon-Seok Han, Sang-Bae Hong, Jin Tae Theranostics Research Paper Rationale: Chitinase 3-like 1 (Chi3L1) protein is up-regulated in various diseases including solid cancers. According to Genome-Wide Association Study (GWAS)/Online Mendelian Inheritance in Man (OMIM)/Differentially Expressed Gene (DEG) analyses, Chi3L1 is associated with 38 cancers, and more highly associated with cancer compared to other oncogenes such as EGFR, TNFα, etc. However, the mechanisms and pathways by which Chi3L1 is associated with cancer are not clear. In current study, we investigated the role of Chi3L1 in lung metastasis. Methods: We performed the differentially expressed gene analysis to explore the genes which are associated with Chi3L1 using the web-based platform from Biomart. We investigated the metastases in lung tissues of C57BL/6 mice injected with B16F10 melanoma following treatment with Ad-shChi3L1. We also investigated the expression of USF1 and Chi3L1 in Chi3L1 KD mice lung tissues by Western blotting and IHC. We also analyzed lung cancer cells metastases induced by Chi3L1 using migration and cell proliferation assay in human lung cancer cell lines. The involvement of miR-125a-3p in Chi3L1 regulation was determined by miRNA qPCR and luciferase reporter assay. Results: We showed that melanoma metastasis in lung tissues was significantly reduced in Chi3L1 knock-down mice, accompanied by down-regulation of MMP-9, MMP-13, VEGF, and PCNA in Chi3L1 knock-down mice lung tissue, as well as in human lung cancer cell lines. We also found that USF1 was conversely expressed against Chi3L1. USF1 was increased by knock-down of Chi3L1 in mice lung tissues, as well as in human lung cancer cell lines. In addition, knock-down of USF1 increased Chi3L1 levels in addition to augmenting metastasis cell migration and proliferation in mice model, as well as in human cancer cell lines. Moreover, in human lung tumor tissues, the expression of Chi3L1 was increased but USF1 was decreased in a stage-dependent manner. Finally, Chi3L1 expression was strongly regulated by the indirect translational suppressing activity of USF1 through induction of miR-125a-3p, a target of Chi3L1. Conclusion: Metastases in mice lung tissues and human lung cancer cell lines were decreased by KD of Chi3L1. USF1 bound to the Chi3L1 promoter, however, Chi3L1 expression was decreased by USF1, despite USF1 enhancing the transcriptional activity of Chi3L1. We found that USF1 induced miR-125a-3p levels which suppressed Chi3L1 expression. Ultimately, our results suggest that lung metastasis is suppressed by knock-down of Chi3L1 through miR-125a-3p-mediated up-regulation of USF1. Ivyspring International Publisher 2018-08-07 /pmc/articles/PMC6134921/ /pubmed/30214629 http://dx.doi.org/10.7150/thno.26467 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Kim, Ki Cheon
Yun, Jaesuk
Son, Dong Ju
Kim, Ji Young
Jung, Jae-Kyung
Choi, Jeong Soon
Kim, Yu Ri
Song, Ju Kyung
Kim, Sun Young
Kang, Sin Kook
Shin, Dae Hwan
Roh, Yoon-Seok
Han, Sang-Bae
Hong, Jin Tae
Suppression of metastasis through inhibition of chitinase 3-like 1 expression by miR-125a-3p-mediated up-regulation of USF1
title Suppression of metastasis through inhibition of chitinase 3-like 1 expression by miR-125a-3p-mediated up-regulation of USF1
title_full Suppression of metastasis through inhibition of chitinase 3-like 1 expression by miR-125a-3p-mediated up-regulation of USF1
title_fullStr Suppression of metastasis through inhibition of chitinase 3-like 1 expression by miR-125a-3p-mediated up-regulation of USF1
title_full_unstemmed Suppression of metastasis through inhibition of chitinase 3-like 1 expression by miR-125a-3p-mediated up-regulation of USF1
title_short Suppression of metastasis through inhibition of chitinase 3-like 1 expression by miR-125a-3p-mediated up-regulation of USF1
title_sort suppression of metastasis through inhibition of chitinase 3-like 1 expression by mir-125a-3p-mediated up-regulation of usf1
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134921/
https://www.ncbi.nlm.nih.gov/pubmed/30214629
http://dx.doi.org/10.7150/thno.26467
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