Bioengineered miR-328-3p modulates GLUT1-mediated glucose uptake and metabolism to exert synergistic antiproliferative effects with chemotherapeutics

Yi, Wanrong; Tu, Mei Juan; Liu, Zhenzhen; Zhang, Chao; Batra, Neelu; Yu, Ai Xi; Yu, Ai Ming

doi:10.1016/j.apsb.2019.11.001

Cited by 59 publications

(55 citation statements)

References 53 publications

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“…Arginine level was determined as recently reported ( Liu et al, 2019 ; Yi et al, 2020 ) with minor modification. Briefly, 200 μl cell lysates (200 ng protein/μl) was added to 800 μl of internal standard (IS) (4-chloro-phenylalanine, 0.05 μM)-containing acetonitrile (ACN) to precipitate the protein, vortexed for 5 minutes, and then centrifuged at 16,000 g for 15 minutes.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-1291-5p Sensitizes Pancreatic Carcinoma Cells to Arginine Deprivation and Chemotherapy through the Regulation of Arginolysis and Glycolysis

Duan

Liu

et al. 2020

Mol Pharmacol

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Cancer cells are dysregulated and addicted to continuous supply and metabolism of nutritional glucose and amino acids (e.g., arginine) to drive the synthesis of critical macromolecules for uncontrolled growth. Recent studies have revealed that genome-derived microRNA-1291-5p (miR-1291-5p or miR-1291) may modulate the expression of argininosuccinate synthase (ASS1) and glucose transporter protein type 1 (GLUT1). We also developed a novel approach to produce recombinant miR-1291 agents for research, which are distinguished from conventional chemo-engineered miRNA mimics. Herein, we firstly demonstrated that bioengineered miR-1291 agent was selectively processed to high levels of target miR-1291-5p in human pancreatic cancer (PC) cells. Following the suppression of ASS1 protein levels, miR-1291 perturbed arginine homeostasis and preferably sensitized ASS1-abundant L3.3 cells to arginine deprivation therapy. In addition, miR-1291 treatment reduced the protein levels of GLUT1 in both AsPC-1 and PANC-1 cells, leading to a lower glucose uptake (deceased > 40%) and glycolysis capacity (reduced approximately 50%). As a result, miR-1291 largely improved cisplatin efficacy in the inhibition of PC cell viability. Our results demonstrated that miR-1291 was effective to sensitize PC cells to arginine deprivation treatment and chemotherapy through targeting ASS1-and GLUT1-mediated arginolysis and glycolysis, respectively, which may provide insights into understanding miRNA signaling underlying cancer cell metabolism and development of new strategies for the treatment of lethal PC.

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Section: Methodsmentioning

confidence: 99%

MicroRNA-1291-5p Sensitizes Pancreatic Carcinoma Cells to Arginine Deprivation and Chemotherapy through the Regulation of Arginolysis and Glycolysis

Duan

Liu

et al. 2020

Mol Pharmacol

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“…Enhanced production of matrix metalloproteinases, including MMP-2, and ECM proteins may lead to tissue remodeling, as well as in the liver. A recent study indicates that miR-328-3p targets GLUT1, leading to a significantly lower glucose uptake and decline in intracellular levels of glucose and lactate [90]. Consequently, a significant miR-328-3p deficiency may increase nutrient uptake, essential for liver steatosis.…”

Section: Discussionmentioning

confidence: 99%

Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis

et al. 2020

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Nutrient excess enhances glucose-dependent insulinotropic polypeptide (GIP) secretion, which may in turn contribute to the development of liver steatosis. We hypothesized that elevated GIP levels in obesity may affect markers of liver injury through microRNAs. The study involved 128 subjects (body mass index (BMI) 25–40). Fasting and postprandial GIP, glucose, insulin, and lipids, as well as fasting alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), cytokeratin-18, fibroblast growth factor (FGF)-19, and FGF-21 were determined. TaqMan low density array was used for quantitative analysis of blood microRNAs. Fasting GIP was associated with ALT [β = 0.16 (confidence interval (CI): 0.01–0.32)], triglycerides [β = 0.21 (95% CI: 0.06–0.36], and FGF-21 [β = 0.20 (95%CI: 0.03–0.37)]; and postprandial GIP with GGT [β = 0.17 (95%CI: 0.03–0.32)]. The odds ratio for elevated fatty liver index (>73%) was 2.42 (95%CI: 1.02–5.72) for high GIP versus low GIP patients. The miRNAs profile related to a high GIP plasma level included upregulated miR-136-5p, miR-320a, miR-483-5p, miR-520d-5p, miR-520b, miR-30e-3p, and miR-571. Analysis of the interactions of these microRNAs with gene expression pathways suggests their potential contribution to the regulation of the activity of genes associated with insulin resistance, fatty acids metabolism, and adipocytokines signaling. Exaggerated fasting and postprandial secretion of GIP in obesity are associated with elevated liver damage markers as well as FGF-21 plasma levels. Differentially expressed microRNAs suggest additional, epigenetic factors contributing to the gut–liver cross-talk.

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“…BERAs produced in living cells have been revealed to carry no or minimal post-transcriptional modifications ( Ponchon and Dardel, 2007 ; Li et al, 2015 ; Wang et al, 2015b ). Although naked BERAs are still susceptible to degradation by serum RNases, BERAs are readily delivered into human carcinoma cells and xenograft tumor tissues by lipid or polymer-based materials; selectively processed to target warhead miRNAs or siRNAs to modulate target gene expression; and consequently inhibit cancer cell proliferation, tumor progression, and metastasis ( Chen et al, 2015 ; Zhao et al, 2016 ; Jian et al, 2017 ; Jilek et al, 2017 , 2019 ; Ho et al, 2018 ; Zhang et al, 2018 ; Li et al, 2019 ; Tu et al, 2019 ; Xu et al, 2019a ; Yi et al, 2020b ). In addition, these BERA-carried miRNAs and siRNAs have been shown to be equally or more effective than synthetic counterparts in the regulation of target gene expression and suppression of cancer cell growth ( Chen et al, 2015 ; Wang et al, 2015b ).…”

Section: Rnas As Therapeutic Drugsmentioning

confidence: 99%

RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges

Yu¹,

Choi²,

Tu³

2020

Pharmacol Rev

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Bioengineered miR-328-3p modulates GLUT1-mediated glucose uptake and metabolism to exert synergistic antiproliferative effects with chemotherapeutics

Cited by 59 publications

References 53 publications

MicroRNA-1291-5p Sensitizes Pancreatic Carcinoma Cells to Arginine Deprivation and Chemotherapy through the Regulation of Arginolysis and Glycolysis

MicroRNA-1291-5p Sensitizes Pancreatic Carcinoma Cells to Arginine Deprivation and Chemotherapy through the Regulation of Arginolysis and Glycolysis

Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis

RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges

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