Dataset Information

Resveratrol and N-acetylcystei reduce hepatic steatosis but enhance initiation and progression of hepatocellular carcinoma

ABSTRACT: we performed longitudinal, unbiased, quantitative proteomics using liver tissues from RES-treated and vehicle-treated DEN/HFD mice

ORGANISM(S): Mus Musculus

SUBMITTER: Chuanrui Xu

PROVIDER: PXD056132 | iProX | Tue Sep 17 00:00:00 BST 2024

REPOSITORIES: iProX

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Publications

Resveratrol and N-acetylcystein reduce hepatic steatosis but enhance initiation and progression of hepatocellular carcinoma by inhibiting GST-pi-MAPK axis in mice.

Zhang Mi M Yuan Weigang W Li Chun C Chen Chanyuan C Liu Xiang X Ma Zhilu Z Xiang Yifei Y Chen Guisha G Wang Chunxu C Li Lei L Wang Lingli L Xu Zhong Z Xu Chuanrui C

Frontiers in pharmacology 20250428

<h4>Introduction</h4>Accumulating evidence indicates that antioxidants promote tumor growth and metastasis after tumor onset in several cancer types. However, whether antioxidants prevent or accelerate hepatic tumorigenesis during steatosis remains unknown. Therefore, we investigated the effects of resveratrol (RES) and N-acetylcysteine (NAC) on hepatocellular carcinoma (HCC) development using two fatty liver mouse models.<h4>Methods</h4>High-fat diet (HFD) plus diethylnitrosamine (DEN)- and AKT ...[more]

PMID: 40356978

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Project description:BackgroundIncreasing evidence has revealed a close relationship between non-coding RNAs and cancer progression. Circular RNAs (circRNAs), a recently identified new member of non-coding RNAs, are demonstrated to participate in diverse biological processes, such as development, homeostatic maintenance and pathological responses. The functions of circRNAs in cancer have drawn wide attention recently. Until now, the expression patterns and roles of circRNAs in hepatocellular carcinoma (HCC) have remained largely unknown.MethodsBioinformatics method was used to screen differentially expressed novel circRNAs in HCC. Northern blotting, qRT-PCR, in situ hybridization (ISH) and RNA-FISH were utilized to analyzed the expression of circRHOT1 in HCC tisues.CCK8, colony formation, EdU assays were used to analyze proliferation of HCC cells. Transwell assay was utilized to analyze HCC cell migration and invasion. FACS was used for apoptosis analysis. Xenograft experiments were used to analyze tumor growth in vivo. Mass spectrum, RNA pulldown, RIP and EMSA was utilized to test the interaction between circRHOT1 and TIP60. RNA-sequencing method was used to analyze the downstream target gene of circRHOT1.ResultsWe identified circRHOT1 (hsa_circRNA_102034) as a conserved and dramatically upregulated circRNA in HCC tissues. HCC patients displaying high circRHOT1 level possessed poor prognosis. Through in vitro and in vivo experiments, we demonstrated circRHOT1 significantly promoted HCC growth and metastasis. Regarding the mechanism, we conducted a RNA pulldown with a biotin-labeled circRHOT1-specific probe and found that circRHOT1 recruited TIP60 to the NR2F6 promoter and initiated NR2F6 transcription. Moreover, NR2F6 knockout inhibited growth, migration and invasion, whereas rescuing NR2F6 in circRHOT1-knockout HCC cells rescued the proliferation and metastasis abilities of HCC cells.ConclusionTaken together, circRHOT1 inhibits HCC development and progression via recruiting TIP60 to initiate NR2F6 expression, indicating that circRHOT1 and NR2F6 may be potential biomarkers for HCC prognosis.

Dataset Information

Resveratrol and N-acetylcystei reduce hepatic steatosis but enhance initiation and progression of hepatocellular carcinoma

Publications

Resveratrol and N-acetylcystein reduce hepatic steatosis but enhance initiation and progression of hepatocellular carcinoma by inhibiting GST-pi-MAPK axis in mice.

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