Quantitative acetylome analysis reveals histone modifications that may predict prognosis in hepatitis B‐related hepatocellular carcinoma

Chai, Xiaoqiang; Dong, Rui‐Zhao; Yang, Xuan; Deng, Chao; Wei, Chuan‐Yuan; Xu, Jiajie; Han, Weiyu; Lu, Jia‐Cheng; Gao, Chao; Gao, Dongmei; Huang, Cheng; Ke, Aiwu; Li, Shuangqi; Li, Huanping; Tian, Yingming; Gu, Zhongkai; Liu, Shuxian; Liu, Hang; Chen, Qilong; Liu, Feng; Zhou, Jian; Fan, Jia; Shi, Guo‐Ming; Wu, Feizhen; Cai, Jia‐Bin

doi:10.1002/ctm2.313

Cited by 25 publications

(21 citation statements)

References 90 publications

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“…We corrected the quantification values corresponding to the acetylated peptide sites using total proteins quantitation values, which avoided misinterpreting possible positive or negative regulations at the protein level as regulations at the residue acetylation level. 21 After normalizing against the total quantitative proteins, 381 up‐regulated Kac sites of 347 DAPs and 319 down‐regulated Kac sites of 238 DAPs were identified between PE and NC placental tissues (Figure 4A ). Notably, among these DAPs, FLNA, FLNB and ACTN4 have multiple Kac sites (Figure 4B ).…”

Section: Resultsmentioning

confidence: 99%

“…Finally, we used 0.1% trifluoroacetic acid to elute the bound Kac peptides from antibody beads. The eluted fractions after vacuum drying were desalted with C18 ZipTips (Merck Millipore) and then analysed by LC‐MS/MS 21 …”

Section: Methodsmentioning

confidence: 99%

“…The eluted fractions after vacuum drying were desalted with C18 ZipTips (Merck Millipore) and then analysed by LC‐MS/MS. 21 …”

Section: Methodsmentioning

confidence: 99%

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Systematic proteomics analysis of lysine acetylation reveals critical features of placental proteins in pregnant women with preeclampsia

Shangguan

Wang

Shi

et al. 2021

J Cellular Molecular Medi

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Preeclampsia (PE) is a dangerous hypertensive disorder that occurs during pregnancy. The specific aetiology and pathogenesis of PE have yet to be clarified. To better reveal the specific pathogenesis of PE, we characterized the proteome and acetyl proteome (acetylome) profile of placental tissue from PE and normal‐term pregnancy by label‐free quantification proteomics technology and PRM analysis. In this research, 373 differentially expressed proteins (DEPs) were identified by proteome analysis. Functional enrichment analysis revealed significant enrichment of DEPs related to angiogenesis and the immune system. COL12A1, C4BPA and F13A1 may be potential biomarkers for PE diagnosis and new therapeutic targets. Additionally, 700 Kac sites were identified on 585 differentially acetylated proteins (DAPs) by acetylome analyses. These DAPs may participate in the occurrence and development of PE by affecting the complement and coagulation cascades pathway, which may have important implications for better understand the pathogenesis of PE. In conclusion, this study systematically analysed the reveals critical features of placental proteins in pregnant women with PE, providing a resource for exploring the contribution of lysine acetylation modification to PE.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Systematic proteomics analysis of lysine acetylation reveals critical features of placental proteins in pregnant women with preeclampsia

Shangguan

Wang

Shi

et al. 2021

J Cellular Molecular Medi

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“…Using MS detection, the acetylation at K194, K211 and K242 of AFP provided novel markers and therapeutic targets for HCC (89). Additionally, the acetylation levels of lysine 120 in histone H2B, lysine 18 in histone H3.3 and lysine 77 in histone H4 were found to be increased in HCC (91). Core histone H3 is another highly conserved protein in cell nucleus and its acetylation has indicated diagnostic significance in HCC (90).…”

Section: Acetylation Of Hccmentioning

confidence: 99%

Potential Biomarkers for Liver Cancer Diagnosis Based on Multi-Omics Strategy

Chen

Wang

et al. 2022

Front. Oncol.

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Liver cancer is the fourth leading cause of cancer-related death worldwide. Hepatocellular carcinoma (HCC) accounts for about 85%-90% of all primary liver malignancies. However, only 20-30% of HCC patients are eligible for curative therapy mainly due to the lack of early-detection strategies, highlighting the significance of reliable and accurate biomarkers. The integration of multi-omics became an important tool for biomarker screening and unique alterations in tumor-associated genes, transcripts, proteins, post-translational modifications and metabolites have been observed. We here summarized the novel biomarkers for HCC diagnosis based on multi-omics technology as well as the clinical significance of these potential biomarkers in the early detection of HCC.

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“…First discovered on attempts to make more efficient hybrid polar compounds that induce the differentiation of transformed cells [19,20] and initially approved by the FDA for the cutanous manifestation of T cell leukemia, vorinostat has since become a therapeutic candidate for many tumors [21][22][23][24][25][26][27][28][29]. This is due in part to the evolving understanding of the role of epigenetic and posttranslational modifications in the etiopathogenesis of transformed cells [30][31][32][33]. Altering many pathways and processes, vorinostat has been discovered to not only alter the modification state of histone proteins but many more essential proteins involved in the oncogenic and tumor suppression process.…”

Section: Introductionmentioning

confidence: 99%

A Knowledge-guided Mechanistic Model of Synthetic Lethality in the HCT116 Vorinostat-resistant Colon Cancer Xenograft Model Cell-line

Aiyetan

2021

Preprint

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With an overall lifetime risk of about 4.3% and 4.0%, in men and women respectively, colorectal cancer remains the third leading cause of cancer-related deaths in the United States. In persons aged 55 and below, its rate increased at 1% per year in the years 2008 to 2017 despite the steady decline associated with improved screening, early diagnosis and treatment in the general population. Besides standardized therapeutic regimen, many trials continue to evaluate the potential benefits of vorinostat, mostly in combination with other anti-neoplastic agents for its treatment. Vorinostat, an FDA approved anti-cancer drug known as suberoylanilide hydroxamic acid (SAHA), an histone deacylase (HDAC) inhibitor, through many mechanisms, causes cancer cell arrest and death. However, like many other anti-neoplastic agents, resistance and or failures have been observed. In the HCT116 colon cancer cell line xenograft model, exploiting potential lethal molecular interactions by additional gene knockouts restored vorinotat sensitivity. This phenomenon, known as synthetic lethality, offers a promise to selectively target cancer cells. Although without clearly delineated understanding of underlying molecular processes, it has been demonstrated as an effective cancer-killing mechanism. In this study, we aimed to elucidate mechanistic interactions in multiple perturbations of identified synthetically lethal experiments, particularly in the vorinostat-resistant HCT116 (colon cancer xenograft model) cell line. Given that previous studies showed that knocking down GLI1, a downstream transcription factor involved in the Sonic Hedgehog pathway -- an embryonal gene regulatory process, resulted in restoration of vorinostat sensitivity in the HCT116 colorectal cancer cell line, we hypothesized that vorinostat resistance is a result of upregulation of embryonal cellular differentiation processes; we hypothesized that elucidated regulatory mechanism would include crosstalks that regulate this biological process. We employed a knowledege-guided fuzzy logic regulatory inference method to elucidate mechanistic relationships. We validated inferred regulatory models in independent datasets. In addition, we evaluated the biomedical significance of key regulatory network genes in an independent clinically annotated dataset. We found no significant evidence that vorinostat resistance is due to an upregulation of embryonal gene regulatory pathways. Our observation rather support a topological rewiring of canonical oncogenic pathways around the PIK3CS, AKT, RAS/BRAF etc. regulatory pathways. Reasoning that significant regulatory network genes are likely implicated in the clinical course of colorectal cancer, we show that the identified key regulatory network genes' expression profile are able to predict short- to medium-term survival in colorectal cancer patients -- providing a rationale basis for prognostification and potentially effective combination of therapeutics that target these genes along with vorinostat in the treatment of colorectal cancer.

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Quantitative acetylome analysis reveals histone modifications that may predict prognosis in hepatitis B‐related hepatocellular carcinoma

Cited by 25 publications

References 90 publications

Systematic proteomics analysis of lysine acetylation reveals critical features of placental proteins in pregnant women with preeclampsia

Systematic proteomics analysis of lysine acetylation reveals critical features of placental proteins in pregnant women with preeclampsia

Potential Biomarkers for Liver Cancer Diagnosis Based on Multi-Omics Strategy

A Knowledge-guided Mechanistic Model of Synthetic Lethality in the HCT116 Vorinostat-resistant Colon Cancer Xenograft Model Cell-line

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