Poly(ADP‐ribosyl)ation is involved in pro‐survival autophagy in porcine blastocysts

Lee, Hye Ran; Gupta, Mukesh Kumar; Kim, Duk Hyeon; Hwang, Jeong Ho; Kwon, Bumsup; Lee, Hoon Taek

doi:10.1002/mrd.22588

Cited by 21 publications

(17 citation statements)

References 49 publications

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“…Autophagy is a self-digestion process in cells, which plays an essential role in cell development and the cellular response to stress [46]. However, excessive autophagy triggers apoptosis-mediated cell death (also a known type of programmed cell death) [47]. Our results showed that the expression of autophagic marker LC3B-II was significantly increased and that of SQSTM1 was significantly reduced in FGSCs after treatment with C28 for 3h, which indicated that C28 induced FGSC autophagy.…”

Section: Discussionmentioning

confidence: 52%

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C28-induced autophagy of female germline stem cells in vitro and its potential mechanisms

Chen¹,

Zhao²,

Tian³

et al. 2019

Preprint

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BackgroundThere are few studies indicating that small molecular compounds affect the proliferation, differentiation, apoptosis, and autophagy of female germline stem cells (FGSCs). However, the epigenetic regulatory mechanism of small molecular compounds that induce autophagy in FGSCs remains unknown.ResultsIn this study, we found that C28 reduced the viability and proliferation of FGSCs, respectively. Additionally, western blotting showed that the expression of autophagy marker light chain 3 beta II (LC3B-II) was significantly increased and expression of sequestosome-1 (SQSTM1) was significantly reduced in C28-treated groups. Immunofluorescence showed that, in C28-treated groups, the number of LC3B-II-positive puncta was increased significantly. These results indicated that C28 induced autophagy of FGSCs in vitro. ChIP-seq data showed that autophagy-related biological processes such as regulation of mitochondrial membrane potential, Golgi vesicle transport, and cellular response to reactive oxygen species were enriched. In addition, RNA-Seq showed that the expression of genes (Trib3, DDIT3, and ATF4) related to endoplasmic reticulum (ER) stress was enhanced by C28.ConclusionC28 could induce FGSC autophagy in vitro leading to a decrease in the number of FGSCs. H3K27ac and ER stress might play roles in C28-induced autophagy of FGSCs in vitro.

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Section: Discussionmentioning

confidence: 52%

“…Data are expressed as the mean ± SEM. Proposed model of the regulatory mechanism of C28-induced autophagy C28 induces autophagy in FGSCs by regulating H3k27ac [45][46][47], and enhances the expression of genes related to ER stress [49][50][51].…”

Section: Statistical Analysesmentioning

confidence: 99%

C28-induced autophagy of female germline stem cells in vitro and its potential mechanisms

Chen¹,

Zhao²,

Tian³

et al. 2019

Preprint

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“…The physiology levels of autophagy are indispensable for blastocyst development in mice [30] and pigs [11]. On the contrary, excessive levels of autophagy are detrimental to blastocyst development [31][32][33].…”

Section: Discussionmentioning

confidence: 99%

“…For instance, ATG5-deleted mouse embryos arrested at the 4-cell stage [10]. Reduced levels of autophagy prevented porcine blastocyst formation [11,12]. It was worth noting that autophagy activity was preferentially restricted to TE cells relative to ICM cells in mouse blastocysts [13].…”

Section: Introductionmentioning

confidence: 99%

METTL3-mediated m6A methylation negatively modulates autophagy to support blastocyst development

Cao

Zhang

Hong

et al. 2020

Preprint

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Background: N6-methyladenosine (m6A) catalyzed by METTL3 regulates the maternal-to-zygotic transition in zebrafish and mice. However, the role and mechanism of METTL3-mediated m6A methylation in blastocyst development remains unclear. Results: We found that reduced m6A levels triggered by METTL3 knockdown caused embryonic arrest during morula-blastocyst transition and developmental defects in trophectoderm cells. Intriguingly, overexpression of METTL3 in early embryos resulted in increased m6A levels and these embryos phenocopied METTL3 knockdown embryos. Mechanistically, METTL3 knockdown or overexpression resulted in a significant increase or decrease in expression of ATG5 and LC3 (an autophagy marker) in blastocysts, respectively. m6A modification of ATG5 mRNA mainly occurs at 3’UTR, and METTL3 knockdown enhanced ATG5 mRNA stability, suggesting that METTL3 negatively regulated autophagy in an m6A dependent manner. Furthermore, single-cell analysis revealed that METTL3 knockdown only increased expression of LC3 and ATG5 in trophectoderm cells, indicating preferential inhibitory effects of METTL3 on autophagy activity in the trophectoderm lineage. Importantly, autophagy restoration by 3MA (an autophagy inhibitor) treatment partially rescued developmental defects of METTL3 knockdown blastocysts. Conclusions: Our results demonstrate that METTL3-mediated m6A methylation negatively modulates autophagy to support blastocyst development.

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“…We detected the levels of different molecules downstream of EGFR and found that the expression of mTOR/p-Akt was significantly different in cancerous and paracancerous tissues, but the expression of PI3K was not different. Poly(ADP)-ribose polymerase-1 (PARP1) repairs single-strand breaks in DNA and is important in autophagy regulation 21 . Reactive oxygen species (ROS) induce PARP1 activity and autophagy, and PARP1 knockout cells display low levels of autophagy, suggesting a prosurvival role for autophagy and PARP1 activity 22 .…”

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confidence: 99%

Role of PARP1-mediated autophagy in EGFR-TKI resistance in non-small cell lung cancer

Zhang

Lian

Xie

et al. 2020

Sci Rep

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Resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has become the main clinical challenge of advanced lung cancer. This research aimed to explore the role of PARP1-mediated autophagy in the progression of TKI therapy. PARP1-mediated autophagy was evaluated in vitro by CCK-8 assay, clonogenic assay, immunofluorescence, and western blot in the HCC-827, H1975, and H1299 cells treated with icotinib (Ico), rapamycin, and AZD2281 (olaparib) alone or in combination. Our results and GEO dataset analysis confirmed that PARP1 is expressed at lower levels in TKI-sensitive cells than in TKI-resistant cells. Low PARP1 expression and high p62 expression were associated with good outcomes among patients with NSCLC after TKI therapy. AZD2281 and a lysosomal inhibitor reversed resistance to Ico by decreasing PARP1 and LC3 in cells, but an mTOR inhibitor did not decrease Ico resistance. The combination of AZD2281 and Ico exerted a markedly enhanced antitumor effect by reducing PARP1 expression and autophagy in vivo. Knockdown of PARP1 expression reversed the resistance to TKI by the mTOR/Akt/autophagy pathway in HCC-827IR, H1975, and H1299 cells. PARP1-mediated autophagy is a key pathway for TKI resistance in NSCLC cells that participates in the resistance to TKIs. Olaparib may serve as a novel method to overcome the resistance to TKIs.

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Poly(ADP‐ribosyl)ation is involved in pro‐survival autophagy in porcine blastocysts

Cited by 21 publications

References 49 publications

C28-induced autophagy of female germline stem cells in vitro and its potential mechanisms

C28-induced autophagy of female germline stem cells in vitro and its potential mechanisms

METTL3-mediated m6A methylation negatively modulates autophagy to support blastocyst development

Role of PARP1-mediated autophagy in EGFR-TKI resistance in non-small cell lung cancer

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