Gene expression profiling reveals U1 snRNA regulates cancer gene expression

Cheng, Zhi; Sun, Yu; Niu, Xiaoran; Shang, Yingchun; Wu, Zhenfeng; Shi, Jin‐Song; Gao, Shan; Zhang, Tao

doi:10.1101/099929

Cited by 6 publications

(20 citation statements)

References 17 publications

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“…Dulbecco's modified Eagle's medium (DMEM) was obtained from Solarbio Science & Technology Co., Ltd. Foetal bovine serum (FBS) and dimethyl sulphoxide (DMSO) were from Dingguo Changsheng Biotechnology Co., Ltd. The purity of 1, 1-Dimethylbiguanide hydrochloride (Metformin) is over 98.0%, purchased from Yuanye Co., Ltd. Aβ [25][26][27][28][29][30][31][32][33][34][35] was synthesized by ChinaPeptides Co., Ltd., and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) was obtained from Amresco. FITC Annexin V Apoptosis Detection Kit was purchased from Beyotime Co., Ltd. l-Glutamic acid (Glu) with a purity ≥99% was obtained from Genview Scientific Inc, and γ-Amino butyric acid (GABA) with a purity ≥99.0% was obtained from Sigma-Aldrich.…”

Section: Chemicalsmentioning

confidence: 99%

“…The culture medium was changed every 3 days. The optimal concentration of Aβ [25][26][27][28][29][30][31][32][33][34][35] and metformin was determined by cell viability applying MTT assay. The experimental groups included control group, the Aβ group and the metformin treatment group (Aβ + met).…”

Section: Cell Culture and Experimental Groupsmentioning

confidence: 99%

“…The experimental groups included control group, the Aβ group and the metformin treatment group (Aβ + met). The SH-SY5Y cells were treated with a concentration of 20 μmol/L Aβ [25][26][27][28][29][30][31][32][33][34][35] for 24 hours to establish an Aβ-treated neurotoxicity model (Aβ group). The metformin treatment group cells were preincubated with 200 μmol/L metformin for 1 hours, and then, 20 μmol/L Aβ [25][26][27][28][29][30][31][32][33][34][35] was added for 24 hours (our preliminary experiment results showed that different concentrations of metformin pretreatment for 1, 6 and 24 hours all rescued the viability decreased by Aβ [25][26][27][28][29][30][31][32][33][34][35] in different degree, and 200 μmol/L for 1 hours of metformin produced the most protective effect, whereas the addition of metformin after Aβ [25][26][27][28][29][30][31][32][33][34][35] had no significant effect on cell viability).…”

Section: Cell Culture and Experimental Groupsmentioning

confidence: 99%

“…Results are expressed relative to GAPDH using the ΔCT method. The qRT-PCR primers were referred to the literature 33,34 and are given in Table 1. SPSS 20 and Origin 8.5 were used to treat and analyse the data.…”

Section: Determination Of Bax Bcl-2 and Lc3 Expression By Western mentioning

confidence: 99%

“…NR2A and NR2B mRNA induced by Aβ [25][26][27][28][29][30][31][32][33][34][35] As shown in Figure 9, the levels of NR2A and NR2B mRNA were significantly increased in the Aβ group (P < 0.01) compared with the control group, and metformin significantly reversed the Aβ-induced change in both the NR2A mRNA (Aβ + met vs Aβ, P < 0.05) and the NR2B mRNA (Aβ + met vs Aβ, P < 0.01). Metformin, a widely used anti-hyperglycaemic agent, has been reported to exert the potentially protective effects in neurodegenerative disease based on related animal models.…”

Section: Metformin Reversed the Increase Inmentioning

confidence: 99%

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Metformin inhibits Aβ_25‐35‐induced apoptotic cell death in SH‐SY5Y cells

Liu

Jiang

et al. 2019

Basic Clin Pharma Tox

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Metformin, a first-line drug for type-2 diabetes, plays a potentially protective role in preventing Alzheimer's disease (AD), but its underlying mechanism is unclear. In this study, Aβ 25-35 -treated SH-SY5Y cells were used as a cell model of AD to investigate the neuroprotective effect of metformin, as well as its underlying mechanisms.We found that metformin decreased the cell apoptosis rate and death, ratio of Bcl-2/ Bax, and expression of NR2A and NR2B, and increased the expression of LC3 in Aβ 25-35 -treated SH-SY5Y cells. Metformin also reduced intracellular and extracellular Glu concentrations, as well as the intracellular concentration of Ca 2+ and ROS in Aβ 25-35 -treated SH-SY5Y cells. These findings suggest that metformin inhibits Aβ 25-35 -treated SH-SY5Y cell death by inhibiting apoptosis, decreasing intracellular Ca 2+ and ROS by reducing neurotoxicity of excitatory amino acids, and by possibly reversing autophagy disorder via regulating autophagy process. K E Y W O R D S apoptosis, Aβ 25-35 , metformin, neuroprotection, toxicity of excitatory amino acids How to cite this article: Li L-X, Liu M-Y, Jiang X, et al. Metformin inhibits Aβ 25-35 -induced apoptotic cell death in SH-SY5Y cells.

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Section: Chemicalsmentioning

confidence: 99%

Section: Cell Culture and Experimental Groupsmentioning

confidence: 99%

Section: Cell Culture and Experimental Groupsmentioning

confidence: 99%

Section: Determination Of Bax Bcl-2 and Lc3 Expression By Western mentioning

confidence: 99%

Section: Metformin Reversed the Increase Inmentioning

confidence: 99%

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Metformin inhibits Aβ_25‐35‐induced apoptotic cell death in SH‐SY5Y cells

Liu

Jiang

et al. 2019

Basic Clin Pharma Tox

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U1 snRNP regulates cancer cell migration and invasion in vitro

et al. 2020

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Stimulated cells and cancer cells have widespread shortening of mRNA 3'-untranslated regions (3'UTRs) and switches to shorter mRNA isoforms due to usage of more proximal polyadenylation signals (PASs) in introns and last exons. U1 snRNP (U1), vertebrates' most abundant non-coding (spliceosomal) small nuclear RNA, silences proximal PASs and its inhibition with antisense morpholino oligonucleotides (U1 AMO) triggers widespread premature transcription termination and mRNA shortening. Here we show that low U1 AMO doses increase cancer cells' migration and invasion in vitro by up to 500%, whereas U1 overexpression has the opposite effect. In addition to 3'UTR length, numerous transcriptome changes that could contribute to this phenotype are observed, including alternative splicing, and mRNA expression levels of proto-oncogenes and tumor suppressors. These findings reveal an unexpected role for U1 homeostasis (available U1 relative to transcription) in oncogenic and activated cell states, and suggest U1 as a potential target for their modulation.

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RNA components of the spliceosome regulate tissue- and cancer-specific alternative splicing

Dvinge

Guenthoer

Porter

et al. 2018

Preprint

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Alternative splicing of pre-mRNAs plays a pivotal role during the establishment and maintenance of human cell types. Characterizing the trans-acting regulatory proteins that control alternative splicing in both healthy and malignant cells has therefore been the focus of much research. Recent work has established that even core protein components of the spliceosome, which are required for splicing to proceed, can nonetheless contribute to splicing regulation by modulating splice site choice. We here demonstrate that the RNA components of the spliceosome likewise influence alternative splicing decisions and contribute to the establishment of global splicing programs. Although these small nuclear RNAs (snRNAs), termed U1, U2, U4, U5, and U6 snRNA, are present in equal stoichiometry within the spliceosome, we found that their relative levels vary by an order of magnitude during development, across tissues, and between normal and malignant cells. Physiologically relevant perturbation of individual snRNAs drove widespread gene-specific differences in alternative splicing, but not transcriptome-wide splicing failure. Genes that were particularly sensitive to variations in snRNA abundance in a breast cancer cell line model were likewise preferentially mis-spliced within a clinically diverse cohort of invasive breast ductal carcinomas. As aberrant mRNA splicing is prevalent in many solid and liquid tumors, we propose that a full understanding of dysregulated pre-mRNA processing in cancers requires study of the RNA as well as protein components of the splicing machinery.

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Gene expression profiling reveals U1 snRNA regulates cancer gene expression

Cited by 6 publications

References 17 publications

Metformin inhibits Aβ_25‐35‐induced apoptotic cell death in SH‐SY5Y cells

Metformin inhibits Aβ_25‐35‐induced apoptotic cell death in SH‐SY5Y cells

U1 snRNP regulates cancer cell migration and invasion in vitro

RNA components of the spliceosome regulate tissue- and cancer-specific alternative splicing

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Gene expression profiling reveals U1 snRNA regulates cancer gene expression

Cited by 6 publications

References 17 publications

Metformin inhibits Aβ25‐35‐induced apoptotic cell death in SH‐SY5Y cells

Metformin inhibits Aβ25‐35‐induced apoptotic cell death in SH‐SY5Y cells

U1 snRNP regulates cancer cell migration and invasion in vitro

RNA components of the spliceosome regulate tissue- and cancer-specific alternative splicing

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Product

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Metformin inhibits Aβ_25‐35‐induced apoptotic cell death in SH‐SY5Y cells

Metformin inhibits Aβ_25‐35‐induced apoptotic cell death in SH‐SY5Y cells