CHML promotes liver cancer metastasis by facilitating Rab14 recycle

Chen, Tianwei; Yin, Fen‐Fen; Yuan, Yang; Guan, Dongxian; Zhang, Er‐Bin; Zhang, Feng-Kun; Jiang, Hao; Ma, Ning; Wang, Jingjing; Ni, Qian‐Zhi; Qiu, Lin; Feng, Jing; Zhang, Xueli; Bao, Ying; Wang, Kang; Cheng, Shuqun; Wang, Xiaofan; Wang, Xiang; Li, Jingjing; Xie, Dong

doi:10.1038/s41467-019-10364-0

Cited by 32 publications

(35 citation statements)

References 53 publications

(49 reference statements)

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“…qPCR was performed according to the protocol of our laboratory 43 , 44 . Briefly, total mRNA was isolated from cultured cells or liver samples using TRIzol reagent (Invitrogen), according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

PPDPF alleviates hepatic steatosis through inhibition of mTOR signaling

Wang

et al. 2021

Nat Commun

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Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease in the world, however, no drug treatment has been approved for this disease. Thus, it is urgent to find effective therapeutic targets for clinical intervention. In this study, we find that liver-specific knockout of PPDPF (PPDPF-LKO) leads to spontaneous fatty liver formation in a mouse model at 32 weeks of age on chow diets, which is enhanced by HFD. Mechanistic study reveals that PPDPF negatively regulates mTORC1-S6K-SREBP1 signaling. PPDPF interferes with the interaction between Raptor and CUL4B-DDB1, an E3 ligase complex, which prevents ubiquitination and activation of Raptor. Accordingly, liver-specific PPDPF overexpression effectively inhibits HFD-induced mTOR signaling activation and hepatic steatosis in mice. These results suggest that PPDPF is a regulator of mTORC1 signaling in lipid metabolism, and may be a potential therapeutic candidate for NAFLD.

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Section: Methodsmentioning

confidence: 99%

PPDPF alleviates hepatic steatosis through inhibition of mTOR signaling

Wang

et al. 2021

Nat Commun

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“…EMHT2 encodes a methyltransferase that is significantly associated with HCC progression and aggression ( Wei et al, 2017 ). CHML promotes HCC metastasis and leads to poor survival, early recurrence, and more satellite nodules ( Chen et al, 2019 ). STK39 contributes to the progression of HCC by the PLK1/ERK signaling pathway ( Zhang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Construction and Validation of Two Hepatocellular Carcinoma-Progression Prognostic Scores Based on Gene Set Variation Analysis

Fan

et al. 2022

Front. Cell Dev. Biol.

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Background: Liver hepatocellular carcinoma (LIHC) remains a global health challenge with a low early diagnosis rate and high mortality. Therefore, finding new biomarkers for diagnosis and prognosis is still one of the current research priorities.Methods: Based on the variation of gene expression patterns in different stages, the LIHC-development genes (LDGs) were identified by differential expression analysis. Then, prognosis-related LDGs were screened out to construct the LIHC-unfavorable gene set (LUGs) and LIHC-favorable gene set (LFGs). Gene set variation analysis (GSVA) was conducted to build prognostic scoring models based on the LUGs and LFGs. ROC curve analysis and univariate and multivariate Cox regression analysis were carried out to verify the diagnostic and prognostic utility of the two GSVA scores in two independent datasets. Additionally, the key LCGs were identified by the intersection analysis of the PPI network and univariate Cox regression and further evaluated their performance in expression level and prognosis prediction. Single-sample GSEA (ssGSEA) was performed to understand the correlation between the two GSVA enrichment scores and immune activity.Result: With the development of LIHC, 83 LDGs were gradually upregulated and 247 LDGs were gradually downregulated. Combining with LIHC survival analysis, 31 LUGs and 32 LFGs were identified and used to establish the LIHC-unfavorable GSVA score (LUG score) and LIHC-favorable GSVA score (LFG score). ROC curve analysis and univariate/multivariate Cox regression analysis suggested the LUG score and LFG score could be great indicators for the early diagnosis and prognosis prediction. Four genes (ESR1, EHHADH, CYP3A4, and ACADL) were considered as the key LCGs and closely related to good prognosis. The frequency of TP53 mutation and copy number variation (CNV) were high in some LCGs. Low-LFG score patients have active metabolic activity and a more robust immune response. The high-LFG score patients characterized immune activation with the higher infiltration abundance of type I T helper cells, DC, eosinophils, and neutrophils, while the high-LUG score patients characterized immunosuppression with the higher infiltration abundance of type II T helper cells, TRegs, and iDC. The high- and low-LFG score groups differed significantly in immunotherapy response scores, immune checkpoints expression, and IC50 values of common drugs.Conclusion: Overall, the LIHC-progression characteristic genes can be great diagnostic and prognostic signatures and the two GSVA score systems may become promising indices for guiding the tumor treatment of LIHC patients.

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“…Thus, the CHML-Rab14 axis has been established as a potential promoter of HCC progression and may be employed as a promising therapeutic target for HCC treatment. 18 , 19 …”

Section: The Molecular Mechanism Of Rab Gtpases As Switches In Membrane Traffickingmentioning

confidence: 99%