UBE2O promotes lipid metabolic reprogramming and liver cancer progression by mediating HADHA ubiquitination

Ma, Ming; Zhang, Changhui; Cao, Rong; Tang, Dongmei; Sang, Xiongbo; Zou, Sailan; Wang, Xiuxuan; Xu, Haixia; Li, Geng; Dai, Lunzhi; Tian, Yan; Gao, Xiang; Fu, Xianghui

doi:10.1038/s41388-022-02509-1

Cited by 11 publications

(8 citation statements)

References 57 publications

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“…HCC accounts for ~90% of primary liver cancer cases and is the third leading cause of cancer-related death globally. [18,19] Although numerous molecules, including noncoding RNAs (ncRNAs), have been found to regulate HCC initiation and progression, [19][20][21][22][23][24] HCC pathogenesis remains incompletely understood. Interestingly, colleagues recently mentioned the existence of eccDNAs in HCC, as shown by computational analysis of WGS data, [2,8] albeit detailed eccDNAs information was lacking.…”

Section: Introductionmentioning

confidence: 99%

Extrachromosomal circular MiR-17-92 amplicon promotes HCC

et al. 2023

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Background and Aims: Extrachromosomal circular DNAs (eccDNAs) are prevalent in cancer genomes and emerge as a class of crucial yet less characterized oncogenic drivers. However, the structure, composition, genomewide frequency, and contribution of eccDNAs in HCC, one of the most fatal and prevalent cancers, remain unexplored. In this study, we provide a comprehensive characterization of eccDNAs in human HCC and demonstrate an oncogenic role of microRNA (miRNA)-17-92-containing eccDNAs in tumor progression.Approach and Results: Using the circle-sequencing method, we identify and characterize more than 230,000 eccDNAs from 4 paired samples of HCC tumor and adjacent nontumor liver tissues. EccDNAs are highly enriched in HCC tumors, preferentially originate from certain chromosomal hotspots, and are correlated with differential gene expression. Particularly, a series of eccDNAs carrying the miRNA-17-92 cluster are validated by outward PCR and Sanger sequencing. Quantitative PCR analyses reveal that miRNA-17-92-containing eccDNAs, along with the expression of their corresponding miRNAs, are elevated in HCC tumors and associated with poor outcomes and the age of HCC patients. More intriguingly, exogenous expression of artificial DNA circles harboring the miR-17-92 cluster, which is synthesized by the ligase-assisted minicircle

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Section: Introductionmentioning

confidence: 99%

Extrachromosomal circular MiR-17-92 amplicon promotes HCC

et al. 2023

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“…The membrane was washed in TBST three times for 5 min each and was developed in Pierce ECL Western Blotting Substrate (Pierce). Regular western blot analysis was performed as described previously 45 . Antibodies for western blot analysis were purchased from Cell Signaling Technology (anti‐Fibrillarin, 2639S; anti‐GAPDH, 5174S; anti‐HSP90, 4877S; anti‐Jun, 9165S; anti‐NPM1, 3542S; anti‐PDI, 2446S; anti‐RPL26, 2065S), Abclonal Technology (anti‐TGFB2, A3640), and Proteintech (anti‐Tubulin, 10068‐1‐AP), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Cell proliferation was measured by MTS (3‐[4,5‐dimethylthiazol‐2‐yl]−5‐[3‐carboxymethoxyphenyl]−2‐[4‐sulfophenyl]−2 H ‐tetrazolium) assay as described previously 45 . In brief, cells were seeded in a 96‐well plate, and rates of cell proliferation were measured by using the CellTiter 96 AQ ueous Nonradioactive Cell Proliferation Assay (Promega).…”

Section: Methodsmentioning

confidence: 99%

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Enhanced nuclear translation is associated with proliferation and progression across multiple cancers

Zou

Kim

Tian

et al. 2023

MedComm

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Recent technological advances have re‐invigorated the interest in nuclear translation (NT), but the underlying mechanisms and functional implications of NT remain unknown. Here we show that NT is enhanced in malignant cancer cells and is associated with rapid cell growth. Nuclear ribopuromycylation analyses in a panel of diverse cell lines revealed that NT is scarce in normal immortalized cells, but is ubiquitous and robust in malignant cancer cells. Moreover, NT occurs in the nucleolus and requires normal nucleolar function. Intriguingly, NT is reduced by cellular stresses and anti‐tumor agents and positively correlates with cancer cell proliferation and growth. By using a modified puromycin‐associated nascent chain proteomics, we further identified numerous oncoproteins that are preferentially translated in the nucleus, such as transforming growth factor‐beta 2 (TGFB2) and nucleophosmin 1 (NMP1). Specific overexpression of TGFB2 and NMP1 messenger RNAs in the nucleus can increase their protein levels and promote tumorigenesis. These findings establish a previously unknown link between NT and malignancy and suggest that cancer cells might have adapted a mechanism of NT to support their need for rapid growth, which highlight the potential of NT in tumorigenesis and might also open up new possibilities for therapeutic targeting of cancer‐specific cellular functions.

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“…Many studies have demonstrated that proteostasis is altered with aging, including the accumulation of unfolded, misfolded, or aggregated proteins. [289][290][291] It is well known that cellular proteome stability is affected by AMPK, mTOR, IIS, and NAD-dependent deacetylases. [292] which could be modulated by fasting.…”

Section: Agingmentioning

confidence: 99%

Fasting: From Physiology to Pathology

Tang

Huang

et al. 2023

Advanced Science

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Overnutrition is a risk factor for various human diseases, including neurodegenerative diseases, metabolic disorders, and cancers. Therefore, targeting overnutrition represents a simple but attractive strategy for the treatment of these increasing public health threats. Fasting as a dietary intervention for combating overnutrition has been extensively studied. Fasting has been practiced for millennia, but only recently have its roles in the molecular clock, gut microbiome, and tissue homeostasis and function emerged. Fasting can slow aging in most species and protect against various human diseases, including neurodegenerative diseases, metabolic disorders, and cancers. These centuried and unfading adventures and explorations suggest that fasting has the potential to delay aging and help prevent and treat diseases while minimizing side effects caused by chronic dietary interventions. In this review, recent animal and human studies concerning the role and underlying mechanism of fasting in physiology and pathology are summarized, the therapeutic potential of fasting is highlighted, and the combination of pharmacological intervention and fasting is discussed as a new treatment regimen for human diseases.

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UBE2O promotes lipid metabolic reprogramming and liver cancer progression by mediating HADHA ubiquitination

Cited by 11 publications

References 57 publications

Extrachromosomal circular MiR-17-92 amplicon promotes HCC

Extrachromosomal circular MiR-17-92 amplicon promotes HCC

Enhanced nuclear translation is associated with proliferation and progression across multiple cancers

Fasting: From Physiology to Pathology

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