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Diagnostic and prognostic values of AKR1C3 and AKR1D1 in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common histological type of primary liver cancer and the majority of patients are diagnosed at an advanced stage and have a poor prognosis. AKR1C3 (Aldo-keto reductase family 1 member C3) and AKR1D1 (Aldo-keto reductase family 1 member D1) catalyze the conv...

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Autores principales: Zhu, Pengfei, Feng, Ruo, Lu, Xu, Liao, Yuan, Du, Zhicheng, Zhai, Wenlong, Chen, Kunlun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906155/
https://www.ncbi.nlm.nih.gov/pubmed/33493134
http://dx.doi.org/10.18632/aging.202380
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author Zhu, Pengfei
Feng, Ruo
Lu, Xu
Liao, Yuan
Du, Zhicheng
Zhai, Wenlong
Chen, Kunlun
author_facet Zhu, Pengfei
Feng, Ruo
Lu, Xu
Liao, Yuan
Du, Zhicheng
Zhai, Wenlong
Chen, Kunlun
author_sort Zhu, Pengfei
collection PubMed
description Hepatocellular carcinoma (HCC) is the most common histological type of primary liver cancer and the majority of patients are diagnosed at an advanced stage and have a poor prognosis. AKR1C3 (Aldo-keto reductase family 1 member C3) and AKR1D1 (Aldo-keto reductase family 1 member D1) catalyze the conversion of aldehydes and ketones to alcohols and play crucial roles in multiple cancers. However, the functions of AKR1C3 and AKR1D1 in HCC remain unclear. In our study, data from the public databases were selected as training and validation sets, then 76 HCC patients in our center were chosen as a test set. Bioinformatics methods suggested AKR1C3 was overexpressed in HCC and AKR1D1 was down-regulated. The receiver operating characteristic curve (ROC) analysis was performed and the area under curve (AUC) values of AKR1C3 and AKR1D1 were above 0.7 (0.948, 0.836, respectively). Also, the high expression of AKR1C3 and low expression of AKR1D1 predicted poor prognosis and short median survival time. Then, the knockdown of AKR1C3 and overexpression of AKR1D1 in HCC cells were achieved with lentivirus. And both decreased cell proliferation, restrained cell viability, and inhibited tumorigenesis. Moreover, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted and the results showed that AKR1C3 and AKR1D1 might participate in the MAPK/ERK and androgen receptor (AR) signaling pathway. Furthermore, the AR and phosphorylated ERK1/2 were significantly reduced after the suppression of AKR1C3 or overexpression of AKR1D1. Collectively, AKR1C3 and AKR1D1 might serve as candidate diagnostic and prognostic biomarkers for HCC and provide potential targets for HCC treatment.
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spelling pubmed-79061552021-03-04 Diagnostic and prognostic values of AKR1C3 and AKR1D1 in hepatocellular carcinoma Zhu, Pengfei Feng, Ruo Lu, Xu Liao, Yuan Du, Zhicheng Zhai, Wenlong Chen, Kunlun Aging (Albany NY) Research Paper Hepatocellular carcinoma (HCC) is the most common histological type of primary liver cancer and the majority of patients are diagnosed at an advanced stage and have a poor prognosis. AKR1C3 (Aldo-keto reductase family 1 member C3) and AKR1D1 (Aldo-keto reductase family 1 member D1) catalyze the conversion of aldehydes and ketones to alcohols and play crucial roles in multiple cancers. However, the functions of AKR1C3 and AKR1D1 in HCC remain unclear. In our study, data from the public databases were selected as training and validation sets, then 76 HCC patients in our center were chosen as a test set. Bioinformatics methods suggested AKR1C3 was overexpressed in HCC and AKR1D1 was down-regulated. The receiver operating characteristic curve (ROC) analysis was performed and the area under curve (AUC) values of AKR1C3 and AKR1D1 were above 0.7 (0.948, 0.836, respectively). Also, the high expression of AKR1C3 and low expression of AKR1D1 predicted poor prognosis and short median survival time. Then, the knockdown of AKR1C3 and overexpression of AKR1D1 in HCC cells were achieved with lentivirus. And both decreased cell proliferation, restrained cell viability, and inhibited tumorigenesis. Moreover, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted and the results showed that AKR1C3 and AKR1D1 might participate in the MAPK/ERK and androgen receptor (AR) signaling pathway. Furthermore, the AR and phosphorylated ERK1/2 were significantly reduced after the suppression of AKR1C3 or overexpression of AKR1D1. Collectively, AKR1C3 and AKR1D1 might serve as candidate diagnostic and prognostic biomarkers for HCC and provide potential targets for HCC treatment. Impact Journals 2021-01-20 /pmc/articles/PMC7906155/ /pubmed/33493134 http://dx.doi.org/10.18632/aging.202380 Text en Copyright: © 2021 Zhu 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
Zhu, Pengfei
Feng, Ruo
Lu, Xu
Liao, Yuan
Du, Zhicheng
Zhai, Wenlong
Chen, Kunlun
Diagnostic and prognostic values of AKR1C3 and AKR1D1 in hepatocellular carcinoma
title Diagnostic and prognostic values of AKR1C3 and AKR1D1 in hepatocellular carcinoma
title_full Diagnostic and prognostic values of AKR1C3 and AKR1D1 in hepatocellular carcinoma
title_fullStr Diagnostic and prognostic values of AKR1C3 and AKR1D1 in hepatocellular carcinoma
title_full_unstemmed Diagnostic and prognostic values of AKR1C3 and AKR1D1 in hepatocellular carcinoma
title_short Diagnostic and prognostic values of AKR1C3 and AKR1D1 in hepatocellular carcinoma
title_sort diagnostic and prognostic values of akr1c3 and akr1d1 in hepatocellular carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906155/
https://www.ncbi.nlm.nih.gov/pubmed/33493134
http://dx.doi.org/10.18632/aging.202380
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