Identification of Glycolysis-Related lncRNAs and the Novel lncRNA WAC-AS1 Promotes Glycolysis and Tumor Progression in Hepatocellular Carcinoma

BackgroundHigh glycolysis efficiency in tumor cells can promote tumor growth. lncRNAs play an important role in the proliferation, metabolism and migration of cancer cells, but their regulation of tumor glycolysis is currently not well researched.MethodsWe analyzed the co-expression of glycolysis-re...

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Main Authors: Xigang Xia, Hao Zhang, Peng Xia, Yimin Zhu, Jie Liu, Kequan Xu, Yufeng Yuan
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-08-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.733595/full
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author Xigang Xia
Xigang Xia
Hao Zhang
Hao Zhang
Peng Xia
Peng Xia
Yimin Zhu
Yimin Zhu
Jie Liu
Jie Liu
Kequan Xu
Kequan Xu
Yufeng Yuan
Yufeng Yuan
author_facet Xigang Xia
Xigang Xia
Hao Zhang
Hao Zhang
Peng Xia
Peng Xia
Yimin Zhu
Yimin Zhu
Jie Liu
Jie Liu
Kequan Xu
Kequan Xu
Yufeng Yuan
Yufeng Yuan
author_sort Xigang Xia
collection DOAJ
description BackgroundHigh glycolysis efficiency in tumor cells can promote tumor growth. lncRNAs play an important role in the proliferation, metabolism and migration of cancer cells, but their regulation of tumor glycolysis is currently not well researched.MethodsWe analyzed the co-expression of glycolysis-related genes and lncRNAs in The Cancer Genome Atlas (TCGA) database to screen glycolysis-related lncRNAs. Further prognostic analysis and differential expression analysis were performed. We further analyzed the relationship between lncRNAs and tumor immune infiltration. Since WAC antisense RNA 1 (WAC-AS1) had the greatest effect on the prognosis among all screened lncRNAs and had a larger coefficient in the prognostic model, we chose WAC-AS1 for further verification experiments and investigated the function and mechanism of action of WAC-AS1 in hepatocellular carcinoma.ResultsWe screened 502 lncRNAs that have co-expression relationships with glycolytic genes based on co-expression analysis. Among them, 112 lncRNAs were abnormally expressed in liver cancer, and 40 lncRNAs were related to the prognosis of patients. Eight lncRNAs (WAC-AS1, SNHG3, SNHG12, MSC-AS1, MIR210HG, PTOV1-AS1, AC145207.5 and AL031985.3) were used to established a prognostic model. Independent prognostic analysis (P<0.001), survival analysis (P<0.001), receiver operating characteristic (ROC) curve analysis (AUC=0.779) and clinical correlation analysis (P<0.001) all indicated that the prognostic model has good predictive power and that the risk score can be used as an independent prognostic factor (P<0.001). The risk score and lncRNAs in the model were found to be related to a variety of immune cell infiltration and immune functions. WAC-AS1 was found to affect glycolysis and promote tumor proliferation (P<0.01). WAC-AS1 affected the expression of several glycolysis-related genes (cAMP regulated phosphoprotein 19 (ARPP19), CHST12, MED24 and KIF2A) (P<0.01). Under hypoxic conditions, WAC-AS1 regulated ARPP19 by sponging miR-320d to promote glucose uptake and lactate production (P<0.01).ConclusionWe constructed a model based on glycolysis-related lncRNAs to evaluate the prognostic risk of patients. The risk score and lncRNAs in the model were related to immune cell infiltration. WAC-AS1 can regulate ARPP19 to promote glycolysis and proliferation by sponging miR-320d.
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spelling doaj.art-b23f221c8fca4fa8b14cca6751d4b77f2022-12-21T22:27:16ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-08-011110.3389/fonc.2021.733595733595Identification of Glycolysis-Related lncRNAs and the Novel lncRNA WAC-AS1 Promotes Glycolysis and Tumor Progression in Hepatocellular CarcinomaXigang Xia0Xigang Xia1Hao Zhang2Hao Zhang3Peng Xia4Peng Xia5Yimin Zhu6Yimin Zhu7Jie Liu8Jie Liu9Kequan Xu10Kequan Xu11Yufeng Yuan12Yufeng Yuan13Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaClinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaClinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaClinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaClinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaClinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaClinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaClinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, ChinaBackgroundHigh glycolysis efficiency in tumor cells can promote tumor growth. lncRNAs play an important role in the proliferation, metabolism and migration of cancer cells, but their regulation of tumor glycolysis is currently not well researched.MethodsWe analyzed the co-expression of glycolysis-related genes and lncRNAs in The Cancer Genome Atlas (TCGA) database to screen glycolysis-related lncRNAs. Further prognostic analysis and differential expression analysis were performed. We further analyzed the relationship between lncRNAs and tumor immune infiltration. Since WAC antisense RNA 1 (WAC-AS1) had the greatest effect on the prognosis among all screened lncRNAs and had a larger coefficient in the prognostic model, we chose WAC-AS1 for further verification experiments and investigated the function and mechanism of action of WAC-AS1 in hepatocellular carcinoma.ResultsWe screened 502 lncRNAs that have co-expression relationships with glycolytic genes based on co-expression analysis. Among them, 112 lncRNAs were abnormally expressed in liver cancer, and 40 lncRNAs were related to the prognosis of patients. Eight lncRNAs (WAC-AS1, SNHG3, SNHG12, MSC-AS1, MIR210HG, PTOV1-AS1, AC145207.5 and AL031985.3) were used to established a prognostic model. Independent prognostic analysis (P<0.001), survival analysis (P<0.001), receiver operating characteristic (ROC) curve analysis (AUC=0.779) and clinical correlation analysis (P<0.001) all indicated that the prognostic model has good predictive power and that the risk score can be used as an independent prognostic factor (P<0.001). The risk score and lncRNAs in the model were found to be related to a variety of immune cell infiltration and immune functions. WAC-AS1 was found to affect glycolysis and promote tumor proliferation (P<0.01). WAC-AS1 affected the expression of several glycolysis-related genes (cAMP regulated phosphoprotein 19 (ARPP19), CHST12, MED24 and KIF2A) (P<0.01). Under hypoxic conditions, WAC-AS1 regulated ARPP19 by sponging miR-320d to promote glucose uptake and lactate production (P<0.01).ConclusionWe constructed a model based on glycolysis-related lncRNAs to evaluate the prognostic risk of patients. The risk score and lncRNAs in the model were related to immune cell infiltration. WAC-AS1 can regulate ARPP19 to promote glycolysis and proliferation by sponging miR-320d.https://www.frontiersin.org/articles/10.3389/fonc.2021.733595/fullhepatocellular carcinomaglycolysisglycolysis-related lncRNAsprognosisWAC-AS1ARPP19
spellingShingle Xigang Xia
Xigang Xia
Hao Zhang
Hao Zhang
Peng Xia
Peng Xia
Yimin Zhu
Yimin Zhu
Jie Liu
Jie Liu
Kequan Xu
Kequan Xu
Yufeng Yuan
Yufeng Yuan
Identification of Glycolysis-Related lncRNAs and the Novel lncRNA WAC-AS1 Promotes Glycolysis and Tumor Progression in Hepatocellular Carcinoma
Frontiers in Oncology
hepatocellular carcinoma
glycolysis
glycolysis-related lncRNAs
prognosis
WAC-AS1
ARPP19
title Identification of Glycolysis-Related lncRNAs and the Novel lncRNA WAC-AS1 Promotes Glycolysis and Tumor Progression in Hepatocellular Carcinoma
title_full Identification of Glycolysis-Related lncRNAs and the Novel lncRNA WAC-AS1 Promotes Glycolysis and Tumor Progression in Hepatocellular Carcinoma
title_fullStr Identification of Glycolysis-Related lncRNAs and the Novel lncRNA WAC-AS1 Promotes Glycolysis and Tumor Progression in Hepatocellular Carcinoma
title_full_unstemmed Identification of Glycolysis-Related lncRNAs and the Novel lncRNA WAC-AS1 Promotes Glycolysis and Tumor Progression in Hepatocellular Carcinoma
title_short Identification of Glycolysis-Related lncRNAs and the Novel lncRNA WAC-AS1 Promotes Glycolysis and Tumor Progression in Hepatocellular Carcinoma
title_sort identification of glycolysis related lncrnas and the novel lncrna wac as1 promotes glycolysis and tumor progression in hepatocellular carcinoma
topic hepatocellular carcinoma
glycolysis
glycolysis-related lncRNAs
prognosis
WAC-AS1
ARPP19
url https://www.frontiersin.org/articles/10.3389/fonc.2021.733595/full
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