Transcriptional and Post-Transcriptional Regulation of Autophagy

Long, Shihui; Gan, Zhending; Tettamanti, Gianluca; Li, Kang; Tian, Ling

doi:10.3390/cells11030441

Cited by 26 publications

(28 citation statements)

References 98 publications

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“…To investigate the influence of autophagy on STAT6 integrity, we examined the fate of the transcription factor in condition conducive to induction of autophagy and used either autophagy inducers or blockers. It is interesting that treatment of cells with Torin1, a bonafide inducer of macroautophagy [ 43 ], exerted no additional effect on STAT6 degradation upon AA starvation, while treatment with established inhibitors of macroautophagy, 3-MA or HCQ, did not block degradation of the transcription factor (Fig. 4 G).…”

Section: Resultsmentioning

confidence: 99%

Promotion of a synthetic degradation of activated STAT6 by PARP-1 inhibition: roles of poly(ADP-ribosyl)ation, calpains and autophagy

et al. 2022

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Background We reported that PARP-1 regulates genes whose products are crucial for asthma, in part, by controlling STAT6 integrity speculatively through a calpain-dependent mechanism. We wished to decipher the PARP-1/STAT6 relationship in the context of intracellular trafficking and promoter occupancy of the transcription factor on target genes, its integrity in the presence of calpains, and its connection to autophagy. Methods This study was conducted using primary splenocytes or fibroblasts derived from wild-type or PARP-1−/− mice and Jurkat T cells to mimic Th2 inflammation. Results We show that the role for PARP-1 in expression of IL-4-induced genes (e.g. gata-3) in splenocytes did not involve effects on STAT6 phosphorylation or its subcellular trafficking, rather, it influenced its occupancy of gata-3 proximal and distal promoters in the early stages of IL-4 stimulation. At later stages, PARP-1 was crucial for STAT6 integrity as its inhibition, pharmacologically or by gene knockout, compromised the fate of the transcription factor. Calpain-1 appeared to preferentially degrade JAK-phosphorylated-STAT6, which was blocked by calpastatin-mediated inhibition or by genetic knockout in mouse fibroblasts. The STAT6/PARP-1 relationship entailed physical interaction and modification by poly(ADP-ribosyl)ation independently of double-strand-DNA breaks. Poly(ADP-ribosyl)ation protected phosphorylated-STAT6 against calpain-1-mediated degradation. Additionally, our results show that STAT6 is a bonafide substrate for chaperone-mediated autophagy in a selective and calpain-dependent manner in the human Jurkat cell-line. The effects were partially blocked by IL-4 treatment and PARP-1 inhibition. Conclusions The results demonstrate that poly(ADP-ribosyl)ation plays a critical role in protecting activated STAT6 during Th2 inflammation, which may be synthetically targeted for degradation by inhibiting PARP-1.

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Section: Resultsmentioning

confidence: 99%

Promotion of a synthetic degradation of activated STAT6 by PARP-1 inhibition: roles of poly(ADP-ribosyl)ation, calpains and autophagy

et al. 2022

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“…LncRNA is a transcribed RNA of more than 200 nucleotides in length that is involved in a range of cell biological processes, including transcription initiation ( 27 ), transcriptional regulation ( 28 ) and chromatin modification ( 29 ). In recent years, an accumulating number of studies have indicated that lncRNAs are closely related to the initiation and progression of many kinds of cancers and have been used in the diagnosis and prognostic analysis of various cancers ( 30 – 33 ).…”

Section: Discussionmentioning

confidence: 99%

The Interferon Gamma-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Colon Adenocarcinoma

Liu

Wang

et al. 2022

Front. Oncol.

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Colon adenocarcinoma (COAD) is one of the most common clinically malignant tumours of the digestive system, with high incidence and mortality and poor prognosis. Interferon-gamma (IFN-γ) and long noncoding RNAs (lncRNAs) have prognostic values and were closely associated with immune microenvironment in COAD. Thus, identifying IFN-γ-related lncRNAs may be valuable in predicting the survival of patients with COAD. In this study, we identified IFN-γ-related lncRNAs and divided COAD patients from the Cancer Genome Atlas (TCGA) database into training and validation sets. Pearson’s correlation analysis and least absolute shrinkage and selection operator (LASSO) Cox regression were performed to select IFN-γ-related lncRNA-associated prognoses. Thirteen lncRNAs (AC025165.8, AC091633.3, FENDRR, LINC00882, LINC01828, LINC01829, MYOSLID, RP11-154H23.4, RP11-20J15.3, RP11-324L17.1, RP11-342A23.2, RP11-805I24.3, SERTAD4-AS1) were identified to construct an IFN-γ-related lncRNA prognostic signature in TCGA training (n =213) and validation (n =213) cohorts. COAD patient risk scores were calculated and classified into high- and low-risk groups based on the median value of the risk scores in each dataset. We compared the overall survival (OS) of patients stratified by age, gender, and stage. The OS in the high-risk group was significantly shorter than that in the low-risk group. In addition, the clinical nomogram incorporating the prognostic signature and clinical features showed a high concordance index of 0.78 and accurately predicted 1-, 3-, and 5-year survival times among COAD patients in the high- and low-risk groups. Based on the risk model, the high- and low-risk groups exhibited distinct differences in the immune system by gene set enrichment analysis (GSEA) functional annotation, and differentially expressed genes (DEGs) between the high- and low-risk groups were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We investigated the expression of multiple immune checkpoint genes in the high- and low-risk groups and plotted Kaplan-Meier survival curves, indicating that immune checkpoint genes, such as LAG3 and PD. L1, STING and TIM 3, were also expressed differently between the two risk groups. Subsequently, there were dramatic differences in mutated genes, SNV (single nucleotide variants) classes, variant types and variant allele frequencies between low- and high-risk patients with COAD. Patients stratified by risk scores had different sensitivities to common chemotherapeutic agents. Finally, we used quantitative real-time polymerase chain reaction (qRT-PCR) assays to demonstrate that three lncRNAs were significantly differentially expressed in COAD tissues and adjacent normal tissues. Considered together, a thirteen-lncRNA prognostic signature has great potential to be a prognostic biomarker and could play an essential role in the immune microenvironment of COAD.

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“…Autophagy is a complex process. Emerging studies have shown that circRNAs can influence disease progression via autophagy regulation, by relying on the transcriptional and post-transcriptional modifications of autophagy-related genes ( 112 ). CircRNAs can regulate autophagy by influencing transcription factors at the RNA level.…”

Section: How Circrnas Influence Disease Progression Through the Regul...mentioning

confidence: 99%

The regulatory roles of circular RNAs via autophagy in ischemic stroke

Li²,

Su³

et al. 2022

Front. Neurol.

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Ischemic stroke (IS) is a severe disease with a high disability, recurrence, and mortality rates. Autophagy, a highly conserved process that degrades damaged or aging organelles and excess cellular components to maintain homeostasis, is activated during IS. It influences the blood–brain barrier integrity and regulates apoptosis. Circular RNAs (circRNAs) are novel non-coding RNAs involved in IS-induced autophagy and participate in various pathological processes following IS. In addition, they play a role in autophagy regulation. This review summarizes current evidence on the roles of autophagy and circRNA in IS and the potential mechanisms by which circRNAs regulate autophagy to influence IS injury. This review serves as a basis for the clinical application of circRNAs as novel biomarkers and therapeutic targets in the future.

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Transcriptional and Post-Transcriptional Regulation of Autophagy

Cited by 26 publications

References 98 publications

Promotion of a synthetic degradation of activated STAT6 by PARP-1 inhibition: roles of poly(ADP-ribosyl)ation, calpains and autophagy

Promotion of a synthetic degradation of activated STAT6 by PARP-1 inhibition: roles of poly(ADP-ribosyl)ation, calpains and autophagy

The Interferon Gamma-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Colon Adenocarcinoma

The regulatory roles of circular RNAs via autophagy in ischemic stroke

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