Nascent Proteome and Glycoproteome Reveal the Inhibition Role of ALG1 in Hepatocellular Carcinoma Cell Migration

Cao, Xinyi; Shao, Yuyin; Meng, Peiyi; Cao, Zhao; Yan, Guoquan; Yao, Jun; Zhou, Xuan‐Wei; Liu, Chao; Zhang, Lei; Shu, Hong; Lu, Haojie

doi:10.1007/s43657-022-00050-5

Cited by 15 publications

(10 citation statements)

References 40 publications

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“…Nevertheless, the median overall survival is only about one year for patients treated with lenvatinib [ 5 ], regorafenib [ 6 ] or cabozantinib [ 7 ]. Numerous studies on HCC pathogenesis have identified potentially novel therapeutic targets [ 8 , 9 ], but these findings have not yet translated into substantially prolonged OS. Therefore, the molecular mechanisms underlying HCC require further detailed elucidation.…”

Section: Introductionmentioning

confidence: 99%

COP9 signalosome complex is a prognostic biomarker and corresponds with immune infiltration in hepatocellular carcinoma

Liu,

Han,

Xuan

et al. 2024

Aging

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Hepatocellular carcinoma (HCC) is among the most common deadly tumors but still lacks specific biomarkers for diagnosis, prognosis, and treatment guidance. The COP9 signalosome (COPS) is an essential regulator of the ubiquitin conjugation pathway upregulated in various cancers. We evaluated the contributions of COPS subunits to HCC tumorigenesis and their utility for prognosis. We comprehensively evaluated the tumor expression pattern and tumorigenic functions of COPS subunits using The Cancer Genome Atlas (TCGA), The Human Protein Atlas and immunohistochemistry. Kaplan–Meier, Cox regression, ROC curve, and nomogram analyses were used to assess the predictive values of COPS subunits for clinical outcome. Expression levels of COPS subunits were significantly upregulated in HCC tissues, which predicted shorter overall survival (OS). Further, Cox regression analysis identified COPS5, COPS7B, and COPS9 as independent prognostic biomarkers for OS. High mutation rates were also found in COPS subunits. Functional network analysis indicated that COPS and neighboring genes regulate ‘protein neddylation’, ‘protein deneddylation’, and ‘protein ubiquitination’. The COPS PPI included strong interactions with p53, CUL1/2/3/4, and JUN. Moreover, the correlations between COPS subunit expression levels and tumor immune cell infiltration rates were examined using TIMER, TISIDB, ssGSEA, and ESTIMATE packages. COPS subunits expression levels were positively correlated with specific tumor immune cell infiltration rates, immunoregulator expression levels, and microsatellite instability in HCC. Finally, knockout of COPS6 and COPS9 in HCC cells reduced while overexpression enhanced proliferation rate and metastasis capacity. Our study revealed that COPS potential biomarker for unfavorable HCC prognosis and indicators of immune infiltration, tumorigenicity, and metastasis.

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Section: Introductionmentioning

confidence: 99%

COP9 signalosome complex is a prognostic biomarker and corresponds with immune infiltration in hepatocellular carcinoma

Liu,

Han,

Xuan

et al. 2024

Aging

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“…Usually, they can be extracted from natural products. Homogenized samples of oligosaccharides and glycoconjugates can also be obtained chemically, enzymatically, or by other biological methods for systematic studies ( Lv, Liu, Hao, Rahman, & Zhang, 2023 ) to translate human bioglycosylation into clinical applications ( Cao et al, 2022 ). However, most oligosaccharides are not destroyed by the body’s stomach acid or broken down by digestive enzymes, but they can be fermented and utilized by bacteria in the intestine to convert them into short-chain fatty acids and lactic acid.…”

Section: Introductionmentioning

confidence: 99%

Preparation, structural characterization, biological activity, and nutritional applications of oligosaccharides

Chen,

Sui,

Wang

et al. 2024

Food Chemistry: X

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“…As HCC is highly heterogeneous, preliminary studies involving proteomic and genomic characterisation can be valuable in understanding the different molecular subtypes and providing personalised treatment options. 4 , 5 , 6 , 7 Transcriptomics and proteomics provide insights into gene and protein expression, while metabolomics offers a functional readout of metabolic processes, allowing for a direct assessment of molecular phenotype and pathophysiological conditions. 8 Dysregulated metabolism is a hallmark of cancer, including HCC.…”

Section: Introductionmentioning

confidence: 99%

Integrative multiomics analysis identifies molecular subtypes and potential targets of hepatocellular carcinoma

Yang,

Zheng,

et al. 2024

Clinical & Translational Med

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BackgroundThe liver is anatomically divided into eight segments based on the distribution of Glisson's triad. However, the molecular mechanisms underlying each segment and its association with hepatocellular carcinoma (HCC) heterogeneity are not well understood. In this study, our objective is to conduct a comprehensive multiomics profiling of the segmentation atlas in order to investigate potential subtypes and therapeutic approaches for HCC.MethodsA high throughput liquid chromatography‐tandem mass spectrometer strategy was employed to comprehensively analyse proteome, lipidome and metabolome data, with a focus on segment‐resolved multiomics profiling. To classify HCC subtypes, the obtained data with normal reference profiling were integrated. Additionally, potential therapeutic targets for HCC were identified using immunohistochemistry assays. The effectiveness of these targets were further validated through patient‐derived organoid (PDO) assays.ResultsA multiomics profiling of 8536 high‐confidence proteins, 1029 polar metabolites and 3381 nonredundant lipids was performed to analyse the segmentation atlas of HCC. The analysis of the data revealed that in normal adjacent tissues, the left lobe was primarily involved in energy metabolism, while the right lobe was associated with small molecule metabolism. Based on the normal reference atlas, HCC patients with segment‐resolved classification were divided into three subtypes. The C1 subtype showed enrichment in ribosome biogenesis, the C2 subtype exhibited an intermediate phenotype, while the C3 subtype was closely associated with neutrophil degranulation. Furthermore, using the PDO assay, exportin 1 (XPO1) and 5‐lipoxygenase (ALOX5) were identified as potential targets for the C1 and C3 subtypes, respectively.ConclusionOur extensive analysis of the segmentation atlas in multiomics profiling defines molecular subtypes of HCC and uncovers potential therapeutic strategies that have the potential to enhance the prognosis of HCC.

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Nascent Proteome and Glycoproteome Reveal the Inhibition Role of ALG1 in Hepatocellular Carcinoma Cell Migration

Cited by 15 publications

References 40 publications

COP9 signalosome complex is a prognostic biomarker and corresponds with immune infiltration in hepatocellular carcinoma

COP9 signalosome complex is a prognostic biomarker and corresponds with immune infiltration in hepatocellular carcinoma

Preparation, structural characterization, biological activity, and nutritional applications of oligosaccharides

Integrative multiomics analysis identifies molecular subtypes and potential targets of hepatocellular carcinoma

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