miR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition

Abstract Tumor metastasis is one of the main causes of hepatocellular carcinoma (HCC) high mortality. CRKL (v-crk sarcoma virus CT10 oncogene homologue (avian)-like) play important roles in tumor metastasis, however, the exact role and underlying mechanism of CRKL in HCC is still unknown. In our stu...

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Autores principales:	Chunmei Guo, Dongting Zhao, Qiuling Zhang, Shuqing Liu, Ming-Zhong Sun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c548e045f43b4c25aa0bf3c4aae63493
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spelling	oai:doaj.org-article:c548e045f43b4c25aa0bf3c4aae634932021-12-02T15:09:06ZmiR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition10.1038/s41598-018-20258-82045-2322https://doaj.org/article/c548e045f43b4c25aa0bf3c4aae634932018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-20258-8https://doaj.org/toc/2045-2322Abstract Tumor metastasis is one of the main causes of hepatocellular carcinoma (HCC) high mortality. CRKL (v-crk sarcoma virus CT10 oncogene homologue (avian)-like) play important roles in tumor metastasis, however, the exact role and underlying mechanism of CRKL in HCC is still unknown. In our study, we demonstrated miR-429 negatively regulated CRKL expression via selectively binding to CRKL-3′-UTR at 3728–3735 bp site by post-transcriptionally mediating its functionality. Re-expression and silencing of miR-429 was remarkably effective in suppressing and promoting HepG2 cell migration and invasion in vitro. Knockdown or overexpression of CRKL exhibited similar effects as the overexpression or silencing of miR-429, whereas, CRKL overexpression (without the 3′-UTR) abrogated miR-429-induced inhibition on HepG2 migration and invasion. Moreover, miR-429-CRKL axis affected HepG2 migration and invasion potentials by regulating the adhesion ability, cytoskeleton F-actin expression and arrangement of HepG2. Furthermore, interference of Raf/MEK/ERK pathway and EMT contributed to miR-429-CRKL axis mediated metastasis inhibition. Nevertheless, miR-429 could not inhibit HepG2 proliferation through CRKL/c-Jun pathway. Taken together, our data demonstrated that miR-429 might function as an antimetastatic miRNA to regulate HCC metastasis by directly targeting CRKL via modulating Raf/MEK/ERK-EMT pathway. The newly identified miR-429-CRKL axis represents a novel potential therapeutic target for HCC treatment.Chunmei GuoDongting ZhaoQiuling ZhangShuqing LiuMing-Zhong SunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-18 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chunmei Guo Dongting Zhao Qiuling Zhang Shuqing Liu Ming-Zhong Sun miR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition
description	Abstract Tumor metastasis is one of the main causes of hepatocellular carcinoma (HCC) high mortality. CRKL (v-crk sarcoma virus CT10 oncogene homologue (avian)-like) play important roles in tumor metastasis, however, the exact role and underlying mechanism of CRKL in HCC is still unknown. In our study, we demonstrated miR-429 negatively regulated CRKL expression via selectively binding to CRKL-3′-UTR at 3728–3735 bp site by post-transcriptionally mediating its functionality. Re-expression and silencing of miR-429 was remarkably effective in suppressing and promoting HepG2 cell migration and invasion in vitro. Knockdown or overexpression of CRKL exhibited similar effects as the overexpression or silencing of miR-429, whereas, CRKL overexpression (without the 3′-UTR) abrogated miR-429-induced inhibition on HepG2 migration and invasion. Moreover, miR-429-CRKL axis affected HepG2 migration and invasion potentials by regulating the adhesion ability, cytoskeleton F-actin expression and arrangement of HepG2. Furthermore, interference of Raf/MEK/ERK pathway and EMT contributed to miR-429-CRKL axis mediated metastasis inhibition. Nevertheless, miR-429 could not inhibit HepG2 proliferation through CRKL/c-Jun pathway. Taken together, our data demonstrated that miR-429 might function as an antimetastatic miRNA to regulate HCC metastasis by directly targeting CRKL via modulating Raf/MEK/ERK-EMT pathway. The newly identified miR-429-CRKL axis represents a novel potential therapeutic target for HCC treatment.
format	article
author	Chunmei Guo Dongting Zhao Qiuling Zhang Shuqing Liu Ming-Zhong Sun
author_facet	Chunmei Guo Dongting Zhao Qiuling Zhang Shuqing Liu Ming-Zhong Sun
author_sort	Chunmei Guo
title	miR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition
title_short	miR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition
title_full	miR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition
title_fullStr	miR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition
title_full_unstemmed	miR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition
title_sort	mir-429 suppresses tumor migration and invasion by targeting crkl in hepatocellular carcinoma via inhibiting raf/mek/erk pathway and epithelial-mesenchymal transition
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/c548e045f43b4c25aa0bf3c4aae63493
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_version_	1718387901293658112

miR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition

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