NUPR1 maintains autolysosomal efflux by activating<i>SNAP25</i>transcription in cancer cells

Mu, Yanchao; Yan, Xiao‐Jie; Li, Ding; Zhao, Dan; Wang, Lingling; Wang, Xiaoyang; Gao, Dan; Yang, Jie; Zhang, Hua; Li, Yanzhe; Sun, Yanan; Wei, Yiliang; Zhang, Zhenfa; Chang, Xinzhong; Yao, Zhi; Tian, Shanshan; Zhang, Kai; Terada, Lance S.; Ma, Zhenyi; Zhe, Liu

doi:10.1080/15548627.2017.1338556

Cited by 85 publications

(91 citation statements)

References 66 publications

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“…10d-f). For example, the expression of EIF4EBP1, NUPR1 and PCK2 with reported oncogenic function involved in the AKT pathway [22][23][24][25] was down-regulated upon circFAM120A knockdown (Extended Data Fig. 10g), supporting its role in promoting cell proliferation.…”

Section: Circfam120a Promotes Cell Growth By Up-regulating Its Parentmentioning

confidence: 88%

Screening for functional circular RNAs using the CRISPR-Cas13 system

Xue³

et al. 2020

Preprint

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Circular RNAs (circRNAs) produced from back-spliced exons are widely expressed, but individual circRNA functions remain poorly understood due to inadequate methods, such as RNAi and genome engineering, in distinguishing overlapped exons in circRNAs from those in linear cognate mRNAs 1,2 . Here we report that the programable RNA-guided, RNA-targeting CRISPR-Cas13, RfxCas13d, effectively and specifically discriminates circRNAs from mRNAs, using guide (g)RNAs targeting sequences spanning the back-splicing junction (BSJ) sites featured in RNA circles. Using a lentiviral library that targets sequences across BSJ sites of highly expressed human circRNAs, we show that a group of circRNAs are important for cell growth mostly in a cell-type specific manner and that a common oncogenic circRNA, circFAM120A, promotes cell proliferation in vitro and in vivo by preventing FAM120A mRNA from binding the translation inhibitor IGF2BP2 for efficient translation. Application of RfxCas13d/BSJ-gRNA screening has also uncovered circMan1a2 with regulatory potential in mouse embryo preimplantation development. Together, these results establish CRISPR-RfxCas13d as a useful tool for the discovery and functional study of circRNAs at both individual and large-scale levels.

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Section: Circfam120a Promotes Cell Growth By Up-regulating Its Parentmentioning

confidence: 88%

Screening for functional circular RNAs using the CRISPR-Cas13 system

Xue³

et al. 2020

Preprint

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“…Moreover, NUPR1 maintains autolysosomal efflux and is required for the progression of non-small cell lung cancer. (15) However, Tang et al (30) have shown that NUPR1 is activated, and mediates intestinal epithelial cells death via increasing autophagy-related gene in response to Shiga toxins toxicity. Consistent with previous reports, the present study demonstrated that quercetin induced NUPR1-dependent autophagic cell death in OS cells.…”

Section: Discussionmentioning

confidence: 99%

“…(13) NUPR1 is required for the optimal expression of metabolic stress-response genes, particularly those involved in DNA repair, cell cycle regulation, apoptosis, entosis and autophagy. (14)(15)(16) Accumulated evidence has led to the integrating hypothesis that activation of NUPR1 transactivates genes necessary for autophagosome formation, autophagosome-lysosome fusion, and cargo degradation. (17) Importantly, under stress full conditions such as chemotherapy treatment, an intricate interplay between the homeostatic NUPR1 and autophagy pathways may occur in cancer cells that will ultimately dictate their fate between cell death or survival.…”

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confidence: 99%

Quercetin induced NUPR1-dependent autophagic cell death by disturbing reactive oxygen species homeostasis in osteosarcoma cells

Zeng

Ouyang

et al. 2020

J. Clin. Biochem. Nutr.

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Osteosarcoma is a primary bone aggressive cancer, affecting adolescents worldwide. Quercetin (a natural polyphenolic com pound) is a polyphenolic flavonoid compound found in a variety of plants. It has been demonstrated to exert cytostatic activity against a variety of human cancer, including the human osteo sarcoma. However, its efficacy in the treatment of osteosarcoma and the underlying antitumor mechanism has not been fully elucidated yet. In this study, we exposed MG 63 cells to different concentrations of quercetin (50, 100 and 200 µM) for 24 h. Here, we show that quercetin increased autophagic flux in the MG 63 cells, as evidenced by the upregulation of LC3B II/LC3B I and downregulation of P62/SQSTM1. Moreover, the autophagy inhibitor Bafilomycin A1 or genetic blocking autophagy with ATG5 knock down decreased quercetin induced cell death, indicating quercetin triggered autophagic cell death in MG 63 cells. Specifically, quercetin increased NUPR1 expression and activated of NUPR1 reporter activity, which contributed to the expression of autophagy related genes and subsequent initiated autophagic cell death in osteo sarcoma cells. Importantly, the increased expression NUPR1 were tightly related to the disturbance of reactive oxygen species (ROS) homeostasis, which could be prevented by inhibiting intracellular ROS with NAC. Finally, NAC also abolished quercetin induced autophagic cell death in vivo. Taken together, these data demon strate that quercetin induces osteosarcoma cell death via inducing excessive autophagy, which is mediated through the ROS NUPR1 pathway. Quercetin application may be a promising and practical strategy for osteosarcoma treatment in clinical practice.

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“…Nupr1 is emerged as an important TF in the growth and migration of human glioblastoma cells [69] and a potent regulator of autolysosomal dynamics via the induction of the SNARE proteins. Nupr1 depletion impairs autolysosomal clearance and induces cytoplasmic vacuolization, suggesting a key role in neuronal autophagy [70,71]. Ccl3 is a known activator of Jak-Stat signaling during prioninduced gliosis [43,72], and deletion of Tnfrsf1 reduces the number of amyloid plaques and cognitive deficits in AD mouse models [73].…”

Section: Discussionmentioning

confidence: 99%

Core transcriptional regulatory circuits in prion diseases

et al. 2020

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Complex diseases involve dynamic perturbations of pathophysiological processes during disease progression. Transcriptional programs underlying such perturbations are unknown in many diseases. Here, we present core transcriptional regulatory circuits underlying early and late perturbations in prion disease. We first identified cellular processes perturbed early and late using time-course gene expression data from three prion-infected mouse strains. We then built a transcriptional regulatory network (TRN) describing regulation of early and late processes. We found over-represented feed-forward loops (FFLs) comprising transcription factor (TF) pairs and target genes in the TRN. Using gene expression data of brain cell types, we further selected active FFLs where TF pairs and target genes were expressed in the same cell type and showed correlated temporal expression changes in the brain. We finally determined core transcriptional regulatory circuits by combining these active FFLs. These circuits provide insights into transcriptional programs for early and late pathophysiological processes in prion disease.

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NUPR1 maintains autolysosomal efflux by activatingSNAP25transcription in cancer cells

Cited by 85 publications

References 66 publications

Screening for functional circular RNAs using the CRISPR-Cas13 system

Screening for functional circular RNAs using the CRISPR-Cas13 system

Quercetin induced NUPR1-dependent autophagic cell death by disturbing reactive oxygen species homeostasis in osteosarcoma cells

Core transcriptional regulatory circuits in prion diseases

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