CUL5–ASB6 Complex Promotes p62/SQSTM1 Ubiquitination and Degradation to Regulate Cell Proliferation and Autophagy

Gong, Liyan; Wang, Qingmin; Wang, Mengcheng; Hu, Ronggui; Li, Huaguang; Gao, Daming; Lin, Moubin

doi:10.3389/fcell.2021.684885

Cited by 10 publications

(7 citation statements)

References 56 publications

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“…Moreover, an increasing number of studies have suggested that SGK1 can regulate the functions of immune cells including T helper cells, and regulatory T cells in the tumor microenvironment ( Sang et al, 2020 ). SQSTM1 (better known as p62), is an autophagy receptor, and its activity mediates multiple biological functions including autophagy, cell growth, and cell death ( Gong et al, 2021 ). Recent studies have demonstrated that SQSTM1 promotes cell growth and induces autophagy in thyroid cancer by modulating AKT/mTOR signaling pathway ( Yu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of an Endoplasmic Reticulum Stress-Related Gene Signature to Evaluate the Immune Status and Predict the Prognosis of Hepatocellular Carcinoma

et al. 2022

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Liver cancer is the sixth most frequently diagnosed primary malignancy and ranks as the third leading cause of cancer-related death worldwide in 2020. ER stress also plays a vital role in the pathogenesis of malignancies. In the current study, we aimed to construct an endoplasmic reticulum stress-related genes (ERGs) signature to predict the overall survival (OS) of patients with HCC. Differentially expressed ERGs (DE-ERGs) were analyzed using The Cancer Genome Atlas (TCGA-LIHC cohort) and International Cancer Genome Consortium (ICGC-LIRI-JP cohort) databases. The prognostic gene signature was identified by the univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox proportional hazards regression analysis. The predictive ability of the model was evaluated by utilizing Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves. Gene set variant analysis (GSVA) was performed to explore the underlying biological processes and signaling pathways. CIBERPORT and single-sample Gene Set Enrichment Analysis (ssGSEA) were implemented to estimate the immune status between the different risk groups. A total of 113 DE-ERGs were identified between 50 normal samples and 365 HCC samples in the TCGA-LIHC cohort, and 48 DE-ERGs were associated with OS through the univariate Cox regression. A six DE-ERGs (PPARGC1A, SQSTM1, SGK1, PON1, CDK1, and G6PD) signature was constructed and classified patients into high-risk and low-risk groups. The risk score was an independent prognostic indicator for OS (HR > 1, p < 0.001). The function enrichment analysis indicated that cell cycle, RNA degradation, protein localization, and cell division were the main biological processes. The high-risk group had higher immune cell infiltration levels than those of the low-risk group. We predicted the response to targeted therapy in high- and low-risk patients with HCC and found that the high-risk patients were more sensitive to pazopanib. At last, we verified the expression of the six gene patterns in HCC tissues by qRT-PCR and immunohistochemistry. This signature may be a potential tool to provide a choice for prognosis prediction and personal management of patients with HCC.

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Section: Discussionmentioning

confidence: 99%

Identification of an Endoplasmic Reticulum Stress-Related Gene Signature to Evaluate the Immune Status and Predict the Prognosis of Hepatocellular Carcinoma

et al. 2022

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“…In fact, studies have shown elevated (53), reduced (54,55) or unchanged (27,56) p62 muscle levels promoted by RT. That controversy may be explained due to the multifunctional role of p62, protein involved in many signal transduction pathways, including nutrition sensing (via mTORC1), inflammation and apoptosis (via NF-kB), antioxidant response (via Nrf2) (57), in addition to autophagy regulation. In fact, studies have demonstrated p62 and Nrf2 are essential for exercise-mediated enhancement of antioxidant protein expression in skeletal muscle (58).…”

Section: Discussionmentioning

confidence: 99%

Resistance Training Attenuates Activation of STAT3 and Muscle Atrophy in Tumor-Bearing Mice

et al. 2022

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PurposeAlthough the role of signal transducers and activators of transcription (STAT3) in cachexia due to the association of circulating IL-6 and muscle wasting has been extensively demonstrated, the effect of resistance training on STAT3 in mediating muscle atrophy in tumor-bearing mice is unknown. The aim of this study is to investigate the effects of resistance exercise training on inflammatory cytokines and oxidative-mediated STAT3 activation and muscle loss prevention in tumor-bearing mice.MethodsMale Swiss mice were inoculated with Ehrlich tumor cells and exposed or not exposed to resistance exercise protocol of ladder climbing. Skeletal muscle STAT3 protein content was measured, compared between groups, and tested for possible association with plasma interleukins and local oxidative stress markers. Components of the ubiquitin-proteasome and autophagy pathways were assessed by real-time PCR or immunoblotting.ResultsResistance training prevented STAT3 excessive activation in skeletal muscle mediated by the overabundance of plasma IL-6 and muscle oxidative stress. These mechanisms contributed to preventing the increased key genes and proteins of ubiquitin-proteasome and autophagy pathways in tumor-bearing mice, such as Atrogin-1, LC3B-II, and Beclin-1. Beyond preventing muscle atrophy, RT also prevented strength loss and impaired locomotor capacity, hallmarks of sarcopenia.ConclusionOur results suggest that STAT3 inhibition is central in resistance exercise protective effects against cancer-induced muscle atrophy and strength loss.

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“…Te ASB6 gene is a novel biomarker and potential therapeutic target in developing oral squamous cell carcinoma, hepatocellular carcinoma, breast cancer, and other tumors. Te ASB6 gene is a risk gene in tumors, and overexpression in various tumors can reduce endoplasmic reticulum stress response, promote flopodia formation, unsuppressed tumor growth, increase metastasis of cancer cells, and poorer patient prognosis [29][30][31][32]. A study confrmed that overexpression of the ASB8 gene in lung cancer has a regulatory efect on tumor cell growth.…”

Section: Discussionmentioning

confidence: 99%

A Survival Model Based on the ASB Genes and Used to Predict the Prognosis of Kidney Renal Clear Cell Carcinoma

et al. 2023

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Kidney renal clear cell carcinoma (KIRC) is increasing in incidence worldwide, with poor and unpredictable patient prognosis limited by diagnostic and therapeutic approaches. New genes are urgently needed to improve this situation. The ankyrin repeat and suppressor of the cytokine signaling (SOCS) box (ASB) family are a promising class of tumorigenesis-related genes. We examined the expression and mutation of 18 ASB genes in various tumors for this study. The findings revealed that ASB genes exhibit significant copy number variation (CNV) and single nucleotide variation (SNV). There were substantial variations in ASB gene expression in different tumor tissues, and different levels of methylation of ASB genes affected the gene expression and tumor progression. By applying LASSO regression analysis, we established a KIRC survival model based on five ASB genes (ASB6, ASB7, ASB8, ASB13, and ASB17). Additionally, ROC curve analysis was used to assess the survival model’s accuracy. Through univariate and multivariate COX regression analysis, we demonstrated that the model’s risk score might be an independent risk factor for individuals with KIRC. In summary, our KIRC survival model could accurately predict patients’ future survival. Further, we also quantified the survival model through a nomogram. This series of findings confirmed that ASB genes are potential predictive markers and targeted therapies for KIRC. Our KIRC survival model based on five ASB genes can help more clinical practitioners make accurate judgments about the prognosis of KIRC patients.

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CUL5–ASB6 Complex Promotes p62/SQSTM1 Ubiquitination and Degradation to Regulate Cell Proliferation and Autophagy

Cited by 10 publications

References 56 publications

Identification of an Endoplasmic Reticulum Stress-Related Gene Signature to Evaluate the Immune Status and Predict the Prognosis of Hepatocellular Carcinoma

Identification of an Endoplasmic Reticulum Stress-Related Gene Signature to Evaluate the Immune Status and Predict the Prognosis of Hepatocellular Carcinoma

Resistance Training Attenuates Activation of STAT3 and Muscle Atrophy in Tumor-Bearing Mice

A Survival Model Based on the ASB Genes and Used to Predict the Prognosis of Kidney Renal Clear Cell Carcinoma

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