Ubiquitin-coated nanodiamonds bind to autophagy receptors for entry into the selective autophagy pathway

Liu, Kuang Kai; Qiu, Wei; Raj, Emmanuel Naveen; Liu, Huei Fang; Huang, Hou Syun; Lin, Yu Wei; Chang, Chien-Jen; Chen, Ting Hua; Chen, Chinpiao; Chang, Huan Cheng; Hwang, Jenn Kang; Ji, Chao

doi:10.1080/15548627.2016.1254864

Cited by 25 publications

(18 citation statements)

References 53 publications

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“…Cellular autophagy can be selectively degraded by autophagy receptors, and then play a role in selectively removing damaged organelles and speci c proteins. p62 (SQSTM1) is a receptor involved in selective autophagy (58), suggesting that autophagy Phagocytosis can play a role in selective degradation.We found that miR-155 may achieve the selectivity for oncoprotein H-Ras by regulating the occurrence of cellular autophagy. Our results show that miR-155 enhances the binding ability of H-Ras and Beclin1, Vps34, Vps15, Uvrage, Bif1, Lamp1, Lamp2, Lamp3, Rubicon, Rab24 in autophagosomes.…”

Section: Discussionmentioning

confidence: 99%

miR155 Enhances Autophagy by Reducing MBD5 and METTL3 in Human Liver Cancer Stem Cells

Lu¹,

Chen²,

Xin³

et al. 2020

Preprint

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Background: miR-155 is a widely reported carcinogenic miRNA, with up-regulated expression in a variety of human cancers. Methods: Liver cancer stem cells were isolated from Huh7 cells; gene infection, RT-PCR, Western blotting and tumorigenesis test in vitro and in vivo were performed to analyze the signaling pathway. Results: we demonstrate that miR-155 inhibits the expression of MBD5 and METTL3 , reducing the expression of DNMT1. In particular, miR155 inhibits the interaction between MBD5 and DNMT1, thereby inhibiting the binding capacity among MBD5, DNMT1 and IGFII (H19 ICR, IGFII DMR, IGFII Enhancer) DNA, inhibiting IGFII DNA methylation modification. Importantly, miR-155 promotes the formation of DNA loops in the IGFII DNA region (H19 ICR-IGFII Enhancer, IGFII DMR-IGFII Enhancer). Therefore, miR155 promotes the binding ability of H19-pre miR675 to histone methyltransferases SUV39h2 dependent on the H19 ICR-IGFII enhancer DNA loop and enhances the methylation modification of histone H3 on the ninth lysine . Then, the binding ability of RNA polII to P300 was enhanced by the formation of H3K9me2-RNA polII-P300 complex. Furthermore, miR155 promotes the binding ability of the RNA PolII-P300 complex to the IGFII promoter dependent on the IGFII DMR-IGFII enhancer DNA loop and promotes the expression of IGFII. Further research shows that miR155 promotes the binding of IGFII to stemness factors and the loading of stemness factors into the promoter region of HGF, which promotes the expression of hepatocyte growth factor HGF. In particular, miR155 promotes the expression of albumin gene (ALB) via HGF-c-MET, and then promotes the Sirt1 expression through ALB. Strikingly, miR155 promotes the autophagy dependent on acetylase Sirt1,including that miR155 promotes LC3 activation dependent on acetylase sirt1 and enhances binding capacity of LC3 to TP53INP2 / DOR, ATG4, ATG3 and ATG7, and the binding ability of the interaction between ATG5, ATG12, ATG6L1, ATG9. More meaningfully, miR155 enhances the ability of H-Ras to bind to the autophagosomes Beclin1, vps34, vps5, Uvrage, bif1, Lamp1, Lamp2, Lamp3, Rubicon, Rab24 dependent on autophagy, thereby enhancing the expression of H-Ras. Furthermore, miR155 enhances the expression of pRaf1, pMEK1 / 2, pERK1 / 2, pElK, pJak, Jun, pAKT, pmTOR, P70S6K, 4E-BP1, SGK1, C-myc dependent on H-Ras.Finally, miR-155 promotes the malignant growth of human liver cancer stem cells mediated by H-Ras.Conclusions: these results provide a valuable theoretical basis for therapeutic targets of liver cancer based on miR-155.

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Section: Discussionmentioning

confidence: 99%

miR155 Enhances Autophagy by Reducing MBD5 and METTL3 in Human Liver Cancer Stem Cells

Lu¹,

Chen²,

Xin³

et al. 2020

Preprint

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“…PTX is a microtubule inhibitor by stabilizing the microtubule polymerization, which leads to mitotic catastrophe 13 – 15 . ND displayed fluorescence property without photobleaching 19 , 24 , 26 , 57 . The intracellular location and uptake ability of ND-PTX can be detected by confocal microscope or flow cytometer.…”

Section: Discussionmentioning

confidence: 99%

“…The intracellular location and uptake ability of ND-PTX can be detected by confocal microscope or flow cytometer. Previously, we showed that ND delivered into lysosomes through the selective autophagy pathway 57 . The uptake ability of ND-PTX is correlated to the anticancer activity of PTX in inducing mitotic catastrophe.…”

Section: Discussionmentioning

confidence: 99%

Co-delivery of paclitaxel and cetuximab by nanodiamond enhances mitotic catastrophe and tumor inhibition

Lin

Raj

Liao

et al. 2017

Sci Rep

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The poor intracellular uptake and non-specific binding of anticancer drugs into cancer cells are the bottlenecks in cancer therapy. Nanocarrier platforms provide the opportunities to improve the drug efficacy. Here we show a carbon-based nanomaterial nanodiamond (ND) that carried paclitaxel (PTX), a microtubule inhibitor, and cetuximab (Cet), a specific monoclonal antibody against epidermal growth factor receptor (EGFR), inducing mitotic catastrophe and tumor inhibition in human colorectal cancer (CRC). ND-PTX blocked the mitotic progression, chromosomal separation, and induced apoptosis in the CRC cells; however, NDs did not induce these effects. Conjugation of ND-PTX with Cet (ND-PTX-Cet) was specifically binding to the EGFR-positive CRC cells and enhanced the mitotic catastrophe and apoptosis induction. Besides, ND-PTX-Cet markedly decreased tumor size in the xenograft EGFR-expressed human CRC tumors of nude mice. Moreover, ND-PTX-Cet induced the mitotic marker protein phospho-histone 3 (Ser10) and apoptotic protein active-caspase 3 for mitotic catastrophe and apoptosis. Taken together, this study demonstrated that the co-delivery of PTX and Cet by ND enhanced the effects of mitotic catastrophe and apoptosis in vitro and in vivo, which may be applied in the human CRC therapy.

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“…Nanoparticles enter cells through phagocytic and non-phagocytic pathways, and finally end with lysosome internalization [13]. Free nanoparticles in the cytoplasm could also be recognized by the autophagy mechanism, researches both in vitro and in vivo showed that intracellular NPs are able to be ubiquitinated or colocalize ubiquitinated protein aggregates, binding to autophagy receptors like p62/SQSTM1, introduce themselves into selective autophagy pathway and facilitate their delivery to lysosome [141,142]. It is worth noting that the autophagic degradation process triggered by NPs does not necessarily strengthen the clearance capacity of cells.…”

Section: The Impacts Of Nps On Autophagosome Maturationmentioning

confidence: 99%

Recent advances in molecular mechanisms of autophagosome-lysosome fusion and impacts of exogenous factors

Zheng¹,

Yuan²,

Xiao³

et al. 2020

ES Food Agrofor.

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Autophagy is a highly conserved phenomenon of cell biology, and it is closely related to many major human diseases such as cancer, neurodegenerative diseases, and diabetes. Autophagy is a continuous biological process, including the formation of autophagosomes, the fusion of autophagosomes and lysosomes, the degradation of substrates, and the regeneration of lysosomes. Relative to the stage of autophagosome formation, there are fewer studies on some of the late processes such as the autophagosomelysosome fusion phase, although some recent advances have been made.Nanoparticles such as silicon and polymeric nanoparticles are being increasingly applied in the electronic and pharmaceutical industries. Recent studies have revealed their role in autophagy and their cytotoxicity. In this review we summarize the current main findings of the molecular mechanisms of the autophagosome-lysosome fusion process and discussed several types of exogenous factors and their impacts on the fusion including protein products of pathogens and nanoparticles. In addition, we indicate remaining questions that need to be addressed in future studies separately in each section.

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Ubiquitin-coated nanodiamonds bind to autophagy receptors for entry into the selective autophagy pathway

Cited by 25 publications

References 53 publications

miR155 Enhances Autophagy by Reducing MBD5 and METTL3 in Human Liver Cancer Stem Cells

miR155 Enhances Autophagy by Reducing MBD5 and METTL3 in Human Liver Cancer Stem Cells

Co-delivery of paclitaxel and cetuximab by nanodiamond enhances mitotic catastrophe and tumor inhibition

Recent advances in molecular mechanisms of autophagosome-lysosome fusion and impacts of exogenous factors

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