Cyclin-Dependent Kinase 4 is expected to be a therapeutic target for hepatocellular carcinoma metastasis using integrated bioinformatic analysis

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Currently, the definitive treatment modality for HCC is radical resection. However, HCC cells possess biological characteristics of high invasion and metastasis. In this respect, to prevent cancer cell i...

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Autores principales:	Jia-Ning Zhang, Feng Wei, Lin-Han Lei, Yang Yang, Yuan Yang, Wei-Ping Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	bioinformatic analysis cdk4 hepatocellular carcinoma (hcc) the cancer genome atlas (tcga) survival analysis invasion and migrationepithelial mesenchymal transition (emt) Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/fb4a896ce90c46138a3e97e811756a58
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spelling	oai:doaj.org-article:fb4a896ce90c46138a3e97e811756a582021-11-26T11:19:50ZCyclin-Dependent Kinase 4 is expected to be a therapeutic target for hepatocellular carcinoma metastasis using integrated bioinformatic analysis2165-59792165-598710.1080/21655979.2021.2006942https://doaj.org/article/fb4a896ce90c46138a3e97e811756a582021-11-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.2006942https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Currently, the definitive treatment modality for HCC is radical resection. However, HCC cells possess biological characteristics of high invasion and metastasis. In this respect, to prevent cancer cell invasion and metastasis and early active intervention, we herein screened through the TCGA database for further prognostic analysis including overall survival (OS) and disease-free survival (DFS). The Kaplan-Meier curve suggested that Cyclin-Dependent Kinase 4 (CDK4) might be an independent prognostic factor for HCC. Moreover, we performed mRNA expression analysis to measure CDK4 levels in normal liver tissues and HCC tissues, and immunohistochemistry (IHC) analysis to detect protein level of CDK4 in Non-tumor tissue and HCC tissues collected from patients. Our findings indicated that the expression of CDK4 was significantly higher in tumor tissues compared with Non-tumor tissue in HCC, which increased from HCC stage 1 to 3. Furthermore, the results of transwell-assay indicated that knocking down CDK4 significantly suppresses the invasion and migration of HCC cells, and the results of bioinformatics analysis revealed that genes closely associated with CDK4 are potentially worthy of further investigation. Additionally, the results of Western Blot indicated CDK4 regulates epithelial mesenchymal transition (EMT) in HCC,and CDK4 appears to regulate EMT and HCC progression via the Wnt/β-catenin pathway. Collectively, this study found the key target gene through bioinformatic analysis and further functional validation through cell experiments. In particular, CDK4 is anticipated to become a crucial hub gene to snipe the metastasis of cancer cells in HCC.Jia-Ning ZhangFeng WeiLin-Han LeiYang YangYuan YangWei-Ping ZhouTaylor & Francis Grouparticlebioinformatic analysiscdk4hepatocellular carcinoma (hcc)the cancer genome atlas (tcga)survival analysisinvasion and migrationepithelial mesenchymal transition (emt)BiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bioinformatic analysis cdk4 hepatocellular carcinoma (hcc) the cancer genome atlas (tcga) survival analysis invasion and migrationepithelial mesenchymal transition (emt) Biotechnology TP248.13-248.65
spellingShingle	bioinformatic analysis cdk4 hepatocellular carcinoma (hcc) the cancer genome atlas (tcga) survival analysis invasion and migrationepithelial mesenchymal transition (emt) Biotechnology TP248.13-248.65 Jia-Ning Zhang Feng Wei Lin-Han Lei Yang Yang Yuan Yang Wei-Ping Zhou Cyclin-Dependent Kinase 4 is expected to be a therapeutic target for hepatocellular carcinoma metastasis using integrated bioinformatic analysis
description	Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Currently, the definitive treatment modality for HCC is radical resection. However, HCC cells possess biological characteristics of high invasion and metastasis. In this respect, to prevent cancer cell invasion and metastasis and early active intervention, we herein screened through the TCGA database for further prognostic analysis including overall survival (OS) and disease-free survival (DFS). The Kaplan-Meier curve suggested that Cyclin-Dependent Kinase 4 (CDK4) might be an independent prognostic factor for HCC. Moreover, we performed mRNA expression analysis to measure CDK4 levels in normal liver tissues and HCC tissues, and immunohistochemistry (IHC) analysis to detect protein level of CDK4 in Non-tumor tissue and HCC tissues collected from patients. Our findings indicated that the expression of CDK4 was significantly higher in tumor tissues compared with Non-tumor tissue in HCC, which increased from HCC stage 1 to 3. Furthermore, the results of transwell-assay indicated that knocking down CDK4 significantly suppresses the invasion and migration of HCC cells, and the results of bioinformatics analysis revealed that genes closely associated with CDK4 are potentially worthy of further investigation. Additionally, the results of Western Blot indicated CDK4 regulates epithelial mesenchymal transition (EMT) in HCC,and CDK4 appears to regulate EMT and HCC progression via the Wnt/β-catenin pathway. Collectively, this study found the key target gene through bioinformatic analysis and further functional validation through cell experiments. In particular, CDK4 is anticipated to become a crucial hub gene to snipe the metastasis of cancer cells in HCC.
format	article
author	Jia-Ning Zhang Feng Wei Lin-Han Lei Yang Yang Yuan Yang Wei-Ping Zhou
author_facet	Jia-Ning Zhang Feng Wei Lin-Han Lei Yang Yang Yuan Yang Wei-Ping Zhou
author_sort	Jia-Ning Zhang
title	Cyclin-Dependent Kinase 4 is expected to be a therapeutic target for hepatocellular carcinoma metastasis using integrated bioinformatic analysis
title_short	Cyclin-Dependent Kinase 4 is expected to be a therapeutic target for hepatocellular carcinoma metastasis using integrated bioinformatic analysis
title_full	Cyclin-Dependent Kinase 4 is expected to be a therapeutic target for hepatocellular carcinoma metastasis using integrated bioinformatic analysis
title_fullStr	Cyclin-Dependent Kinase 4 is expected to be a therapeutic target for hepatocellular carcinoma metastasis using integrated bioinformatic analysis
title_full_unstemmed	Cyclin-Dependent Kinase 4 is expected to be a therapeutic target for hepatocellular carcinoma metastasis using integrated bioinformatic analysis
title_sort	cyclin-dependent kinase 4 is expected to be a therapeutic target for hepatocellular carcinoma metastasis using integrated bioinformatic analysis
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/fb4a896ce90c46138a3e97e811756a58
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_version_	1718409510535561216

Cyclin-Dependent Kinase 4 is expected to be a therapeutic target for hepatocellular carcinoma metastasis using integrated bioinformatic analysis

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