Lysine Acetylome Study of Human Hepatocellular Carcinoma Tissues for Biomarkers and Therapeutic Targets Discovery
Lysine acetylation is a vital post-translational modification (PTM) of proteins, which plays an important role in cancer development. In healthy human liver tissues, multiple non-histone proteins were identified with acetylation modification, however, the role of acetylated proteins in hepatocellula...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-09-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2020.572663/full |
| _version_ | 1818525083599110144 |
|---|---|
| author | Qianwei Zhao Qianwei Zhao Zhendong Zhang Jinxia Li Fang Xu Bingxia Zhang Mengduan Liu Yixian Liu Huiping Chen Junxia Yang Jintao Zhang |
| author_facet | Qianwei Zhao Qianwei Zhao Zhendong Zhang Jinxia Li Fang Xu Bingxia Zhang Mengduan Liu Yixian Liu Huiping Chen Junxia Yang Jintao Zhang |
| author_sort | Qianwei Zhao |
| collection | DOAJ |
| description | Lysine acetylation is a vital post-translational modification (PTM) of proteins, which plays an important role in cancer development. In healthy human liver tissues, multiple non-histone proteins were identified with acetylation modification, however, the role of acetylated proteins in hepatocellular carcinoma (HCC) development remains largely unknown. Here we performed a quantitative acetylome study of tumor and normal liver tissues from HCC patients. Overall, 598 lysine acetylation sites in 325 proteins were quantified, and almost 59% of their acetylation levels were significantly changed. The differentially acetylated proteins mainly consisted of non-histone proteins located in mitochondria and cytoplasm, which accounted for 42% and 24%, respectively. Bioinformatics analysis showed that differentially acetylated proteins were enriched in metabolism, oxidative stress, and signal transduction processes. In tumor tissues, 278 lysine sites in 189 proteins showed decreased acetylation levels, which occupied 98% of differentially acetylated proteins. Moreover, we collected twenty pairs of tumor and normal liver tissues from HCC male patients, and found that expression levels of SIRT1 (p = 0.002), SIRT2 (p = 0.01), and SIRT4 (p = 0.045) were significantly up-regulated in tumor tissues. Over-expression of possibly accounted for the widespread deacetylation of non-histone proteins identified in HCC tumor tissues, which could serve as promising predictors of HCC. Taken together, our work illustrates abundant differentially acetylated proteins in HCC tumor tissues, and offered insights into the role of lysine acetylation in HCC development. It provided potential biomarker and drug target candidates for clinical HCC diagnosis and treatment. |
| first_indexed | 2024-12-11T06:05:02Z |
| format | Article |
| id | doaj.art-40f4f0767cb64f27a39123f4ec240930 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-11T06:05:02Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-40f4f0767cb64f27a39123f4ec2409302022-12-22T01:18:19ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-09-011110.3389/fgene.2020.572663572663Lysine Acetylome Study of Human Hepatocellular Carcinoma Tissues for Biomarkers and Therapeutic Targets DiscoveryQianwei Zhao0Qianwei Zhao1Zhendong Zhang2Jinxia Li3Fang Xu4Bingxia Zhang5Mengduan Liu6Yixian Liu7Huiping Chen8Junxia Yang9Jintao Zhang10BGI College and Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory for Pharmacology of Liver Diseases, Zhengzhou University, Zhengzhou, ChinaBGI College and Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaSchool of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaBGI College and Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou, ChinaBGI College and Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaBGI College and Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaBGI College and Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaBGI College and Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaBGI College and Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, ChinaLysine acetylation is a vital post-translational modification (PTM) of proteins, which plays an important role in cancer development. In healthy human liver tissues, multiple non-histone proteins were identified with acetylation modification, however, the role of acetylated proteins in hepatocellular carcinoma (HCC) development remains largely unknown. Here we performed a quantitative acetylome study of tumor and normal liver tissues from HCC patients. Overall, 598 lysine acetylation sites in 325 proteins were quantified, and almost 59% of their acetylation levels were significantly changed. The differentially acetylated proteins mainly consisted of non-histone proteins located in mitochondria and cytoplasm, which accounted for 42% and 24%, respectively. Bioinformatics analysis showed that differentially acetylated proteins were enriched in metabolism, oxidative stress, and signal transduction processes. In tumor tissues, 278 lysine sites in 189 proteins showed decreased acetylation levels, which occupied 98% of differentially acetylated proteins. Moreover, we collected twenty pairs of tumor and normal liver tissues from HCC male patients, and found that expression levels of SIRT1 (p = 0.002), SIRT2 (p = 0.01), and SIRT4 (p = 0.045) were significantly up-regulated in tumor tissues. Over-expression of possibly accounted for the widespread deacetylation of non-histone proteins identified in HCC tumor tissues, which could serve as promising predictors of HCC. Taken together, our work illustrates abundant differentially acetylated proteins in HCC tumor tissues, and offered insights into the role of lysine acetylation in HCC development. It provided potential biomarker and drug target candidates for clinical HCC diagnosis and treatment.https://www.frontiersin.org/article/10.3389/fgene.2020.572663/fullhepatocellular carcinomalysine acetylationnon-histone proteinssirtuinsbiomarker candidatesdrug discovery |
| spellingShingle | Qianwei Zhao Qianwei Zhao Zhendong Zhang Jinxia Li Fang Xu Bingxia Zhang Mengduan Liu Yixian Liu Huiping Chen Junxia Yang Jintao Zhang Lysine Acetylome Study of Human Hepatocellular Carcinoma Tissues for Biomarkers and Therapeutic Targets Discovery Frontiers in Genetics hepatocellular carcinoma lysine acetylation non-histone proteins sirtuins biomarker candidates drug discovery |
| title | Lysine Acetylome Study of Human Hepatocellular Carcinoma Tissues for Biomarkers and Therapeutic Targets Discovery |
| title_full | Lysine Acetylome Study of Human Hepatocellular Carcinoma Tissues for Biomarkers and Therapeutic Targets Discovery |
| title_fullStr | Lysine Acetylome Study of Human Hepatocellular Carcinoma Tissues for Biomarkers and Therapeutic Targets Discovery |
| title_full_unstemmed | Lysine Acetylome Study of Human Hepatocellular Carcinoma Tissues for Biomarkers and Therapeutic Targets Discovery |
| title_short | Lysine Acetylome Study of Human Hepatocellular Carcinoma Tissues for Biomarkers and Therapeutic Targets Discovery |
| title_sort | lysine acetylome study of human hepatocellular carcinoma tissues for biomarkers and therapeutic targets discovery |
| topic | hepatocellular carcinoma lysine acetylation non-histone proteins sirtuins biomarker candidates drug discovery |
| url | https://www.frontiersin.org/article/10.3389/fgene.2020.572663/full |
| work_keys_str_mv | AT qianweizhao lysineacetylomestudyofhumanhepatocellularcarcinomatissuesforbiomarkersandtherapeutictargetsdiscovery AT qianweizhao lysineacetylomestudyofhumanhepatocellularcarcinomatissuesforbiomarkersandtherapeutictargetsdiscovery AT zhendongzhang lysineacetylomestudyofhumanhepatocellularcarcinomatissuesforbiomarkersandtherapeutictargetsdiscovery AT jinxiali lysineacetylomestudyofhumanhepatocellularcarcinomatissuesforbiomarkersandtherapeutictargetsdiscovery AT fangxu lysineacetylomestudyofhumanhepatocellularcarcinomatissuesforbiomarkersandtherapeutictargetsdiscovery AT bingxiazhang lysineacetylomestudyofhumanhepatocellularcarcinomatissuesforbiomarkersandtherapeutictargetsdiscovery AT mengduanliu lysineacetylomestudyofhumanhepatocellularcarcinomatissuesforbiomarkersandtherapeutictargetsdiscovery AT yixianliu lysineacetylomestudyofhumanhepatocellularcarcinomatissuesforbiomarkersandtherapeutictargetsdiscovery AT huipingchen lysineacetylomestudyofhumanhepatocellularcarcinomatissuesforbiomarkersandtherapeutictargetsdiscovery AT junxiayang lysineacetylomestudyofhumanhepatocellularcarcinomatissuesforbiomarkersandtherapeutictargetsdiscovery AT jintaozhang lysineacetylomestudyofhumanhepatocellularcarcinomatissuesforbiomarkersandtherapeutictargetsdiscovery |