Chaperone-mediated autophagy regulates apoptosis and the proliferation of colon carcinoma cells

Peng, Jieqiong; Han, Sileny; Chen, Ze-hao; Yang, Jing; Pei, Yan; Bao, Cong; Qiao, Li; Chen, Wenqiang; Liu, Bo

doi:10.1016/j.bbrc.2019.11.081

Cited by 24 publications

(25 citation statements)

References 24 publications

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“…The lysossomal associated protein 2a (LAMP-2A) is a key regulatory protein in the chaperonmediated autophagy(CMA) pathway. Inhibiting the LAMP-2A protein can speci cally block the CMA pathway [26].…”

Section: Disease Progression Of Mrl/lpr Lupus Mice After Experimental Intervention Of Mir-99a-3p In Vivomentioning

confidence: 99%

WITHDRAWN: miR-99a-3p Targeting EIF4EBP1 Affects B Lymphocytes Function Through Autophagy and Aggravates SLE Disease Progression

Yang

Deng

2021

Preprint

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Background:Overactivation of immune cells plays a key role in the pathogenesis of systemic lupus erythematosus (SLE). The regulation of immune cells by miRNA is a research hotspot.In this study, the second-generation high-throughput sequencing found that the expression of miR-99a-3p in SLE decreased, but the specific mechanism is still unclear.The purpose of this study is to explore the potential target genes, target cells of miR-99a-3p and their potential mechanisms affecting the progression of SLE.Methods: Isolate PBMC from healthy individulas and SLE patients, transfect Ball-1, Jurkat, THP-1 and K562 cells with miR-99a-3p agomir and antagomir,detect miR-99a-3p, predict target genes and autophagy pathway mRNA and protein expression by RT-qPCR and Western blotting.CCK-8 method detects cell proliferation, PI method detects cell cycle, flow cytometry detects cell apoptosis, and luciferase reporter gene experiment determines miR-99a-3p target genes.With C57BL/6J mice as control,construct miR-99a-3p overexpression and interference model based on MRL/lpr mice,ELISA detects plasma ANA, dsDNA, IgE, IgM, IL-6, IL-10, BLyS.Pathological analysis of HE staining and C3 immunofluorescence(IF) deposition in mouse kidney tissue,Immunohistochemistry(IHC) detects changes in target genes and pathway proteins in kidney tissue,isolate B cells to verify the differential expression of miR-99a-3p, target genes, pathway mRNA and protein.Results: Compared with healthy individulas, miR-99a-3p in SLE was down-regulated, while EIF4EBP1, LC3II, LAMP-2A mRNA and protein expression were up-regulated.After Ball-1 was transfected with miR-99a-3p agomir, cell proliferation decreased and apoptosis increased.After transfected with miR-99a-3p antagomir, the effect was opposite;Luciferase reporter gene detection proved that miR-99a-3p directly targets EIF4EBP1. Rescue experiments confirmed the interaction model between miR-99a-3p and EIF4EBP1. Clinical, in vitro, and in vivo experiments further confirmed that miR-99a-3p agomir can reduce the expression of EIF4EBP1, LC3-Ⅱ, and LAMP-2A, while miR-99a-3p antagomir had the opposite effect.In vivo experiment antagomir group mice serum ANA, dsDNA, IgE, IgM, IL-6, IL-10, BLyS were higher than those in the MRL/lpr group, EIF4EBP1, LC3-Ⅱ, LAMP-2A mRNA, protein and IHC levels also increased, and the urinary protein and C3 IF deposition of mice in the antagomir group were increased, and the related indexes of mice in the agomir group were lower than those in the MRL/lpr group.Conclusion:The expression of miR-99a-3p in SLE PBMC was down-regulated. Up-regulation of miR-99a-3p by transfection can protect B cells from autophagy mediated by EIF4EBP1.The down-regulation of miR-99a-3p induces autophagy by regulating the autophagy signaling pathway mediated by EIF4EBP1 in SLE B cells. These results indicate that miR-99a-3p and EIF4EBP1 may be potential targets of SLE.

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Section: Disease Progression Of Mrl/lpr Lupus Mice After Experimental Intervention Of Mir-99a-3p In Vivomentioning

confidence: 99%

WITHDRAWN: miR-99a-3p Targeting EIF4EBP1 Affects B Lymphocytes Function Through Autophagy and Aggravates SLE Disease Progression

Yang

Deng

2021

Preprint

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“…CMA activity is markedly increased in cancer cells. Noteworthy, an anti-or pro-cancer function of CMA appears to depend, at least in some extent, on the status of cell transformation (83) and stage of the specific tumor (84,85). This facet supports the importance of a context-dependent therapy investigation, requiring specialized research and a more translational approach.…”

Section: Chaperone-mediated Autophagy In Glioblastomamentioning

confidence: 88%

Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma

et al. 2020

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“…LAMP‐2A is a key regulatory protein in the chaperone‐mediated autophagy (CMA) pathway. Inhibition of the expression of the LAMP‐2A protein specifically blocks the CMA pathway 25 …”

Section: Discussionmentioning

confidence: 99%

Targeting of EIF4EBP1 by miR‐99a‐3p affects the functions of B lymphocytes via autophagy and aggravates SLE disease progression

Yang

Deng

2021

J Cellular Molecular Medi

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Excessive activation of immune cells plays a key role in the pathogenesis of systemic lupus erythematosus (SLE). The regulation of immune cells by miRNAs is a research hotspot. In this study, second‐generation high‐throughput sequencing revealed a reduction in miR‐99a‐3p expression in patients with SLE; however, the specific mechanism underlying this phenomenon remains unclear. After transfection with an miR‐99a‐3p agomir, the proliferation of Ball‐1 cells decreased and the levels of their apoptosis increased. The opposite effects were observed in cells transfected with the miR‐99a‐3p antagomir. Luciferase reporter assay indicated that miR‐99a‐3p directly targeted EIF4EBP1. Rescue experiments confirmed the proposed interaction between miR‐99a‐3p and EIF4EBP1. In vitro, in vivo and clinical investigations further confirmed that the miR‐99a‐3p agomir reduced the expression of EIF4EBP1, LC3B and LAMP‐2A. In the in vivo experiments, serum levels of anti‐nuclear antibodies, double‐stranded DNA, IgE, IgM, IL‐6, IL‐10 and B lymphocyte stimulator were higher in mice from the antagomir group than those in mice from the MRL/lpr group. Furthermore, the protein and mRNA levels of EIF4EBP1, LC3B and LAMP‐2A, the intensity of immunohistochemical staining of EIF4EBP1, LC3B and LAMP‐2A, the urinary protein levels, and the C3 immunofluorescence deposition increased in mice from the antagomir group. The upregulation of miR‐99a‐3p expression protected B cells from EIF4EBP1‐mediated autophagy, whilst the downregulation of miR‐99a‐3p expression induced autophagy via the EIF4EBP1‐mediated regulation of the autophagy signalling pathway in B cells isolated from individuals with SLE. Based on these results, miR‐99a‐3p and EIF4EBP1 may be considered potential targets for SLE treatment.

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Chaperone-mediated autophagy regulates apoptosis and the proliferation of colon carcinoma cells

Cited by 24 publications

References 24 publications

WITHDRAWN: miR-99a-3p Targeting EIF4EBP1 Affects B Lymphocytes Function Through Autophagy and Aggravates SLE Disease Progression

WITHDRAWN: miR-99a-3p Targeting EIF4EBP1 Affects B Lymphocytes Function Through Autophagy and Aggravates SLE Disease Progression

Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma

Targeting of EIF4EBP1 by miR‐99a‐3p affects the functions of B lymphocytes via autophagy and aggravates SLE disease progression

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