circ_CSNK1E modulates airway smooth muscle cells proliferation and migration via miR-34a-5p/VAMP2 axis in asthma

Ding, Ling; Liu, Guangling; Lu, Lu; Liu, Ge; Wang, Jinya

doi:10.1016/j.cellsig.2022.110340

Cited by 11 publications

(11 citation statements)

References 26 publications

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“…Moreover, we did not observe any change in the expression of GLUT4 and GLUT1 in adipocytes following miR-34a overexpression, which could have been another mechanism by which miR-34a would have decreased glucose uptake. This downregulation of VAMP2 is consistent with studies showing that VAMP2 is a direct target of miR-34a in different cell types, including pancreatic beta cells [ 26 , 48 , 49 ]. Interestingly, it is plausible that miRs negatively control the expression of VAMP2 in adipocytes during obesity because its expression was markedly reduced in eAT of obese mice without significant change in its mRNA level.…”

Section: Discussionsupporting

confidence: 91%

The Stress-Responsive microRNA-34a Alters Insulin Signaling and Actions in Adipocytes through Induction of the Tyrosine Phosphatase PTP1B

Cornejo

Vergoni

Angot

et al. 2022

Cells

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Metabolic stresses alter the signaling and actions of insulin in adipocytes during obesity, but the molecular links remain incompletely understood. Members of the microRNA-34 (miR-34 family play a pivotal role in stress response, and previous studies showed an upregulation of miR-34a in adipose tissue during obesity. Here, we identified miR-34a as a new mediator of adipocyte insulin resistance. We confirmed the upregulation of miR-34a in adipose tissues of obese mice, which was observed in the adipocyte fraction exclusively. Overexpression of miR-34a in 3T3-L1 adipocytes or in fat pads of lean mice markedly reduced Akt activation by insulin and the insulin-induced glucose transport. This was accompanied by a decreased expression of VAMP2, a target of miR-34a, and an increased expression of the tyrosine phosphatase PTP1B. Importantly, PTP1B silencing prevented the inhibitory effect of miR-34a on insulin signaling. Mechanistically, miR-34a decreased the NAD+ level through inhibition of Naprt and Nampt, resulting in an inhibition of Sirtuin-1, which promoted an upregulation of PTP1B. Furthermore, the mRNA expression of Nampt and Naprt was decreased in adipose tissue of obese mice. Collectively, our results identify miR-34a as a new inhibitor of insulin signaling in adipocytes, providing a potential pathway to target to fight insulin resistance.

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Section: Discussionsupporting

confidence: 91%

The Stress-Responsive microRNA-34a Alters Insulin Signaling and Actions in Adipocytes through Induction of the Tyrosine Phosphatase PTP1B

Cornejo

Vergoni

Angot

et al. 2022

Cells

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“…Moreover, hsa-miR-34a-5p was found down-regulated in exosomes derived from the bronchial epithelial cells stimulated by inflammatory factors [51]. In addition, Ding et al [52] indicated that hsa-miR-34a-5p suppressed proliferation and migration in an in vitro model of airway smooth muscle cells, a key process of airway remodeling in asthma. Similarly, hsa-miR-181a-5p trended oppositely between asthmatics and obese, suggesting a decrease in asthma and an increase in obesity, despite mixed literature data [53][54][55].…”

Section: Discussionmentioning

confidence: 99%

Circulating MicroRNAs Expression Profile in Lung Inflammation: A Preliminary Study

Mirra

Cione

Spaziano

et al. 2022

JCM

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Background: Bronchial asthma is an inflammatory airway disease with an ever-increasing incidence. Therefore, innovative management strategies are urgently needed. MicroRNAs are small molecules that play a key role in lungs cellular functions and are involved in chronic inflammatory diseases, such as bronchial asthma. This study aims to compare microRNA serum expression between subjects with asthma, obesity, the most common co-morbidity in asthma, and healthy controls to obtain a specific expression profile specifically related to lung inflammation. Methods: We collected serum samples from a prospective cohort of 25 sex-matched subjects to determine circulating miRNAs through a quantitative RT-PCR. Moreover, we performed an in silico prediction of microRNA target genes linked to lung inflammation. Results: Asthmatic patients had a significant lower expression of hsa-miR-34a-5p, 181a-5p and 146a-5p compared to both obese and healthy ones suggesting microRNAs’ specific involvement in the regulation of lungs inflammatory response. Indeed, using in silico analysis, we identified microRNAs novel target genes as GATA family, linked to the inflammatory-related pathway. Conclusions: This study identifies a novel circulating miRNAs expression profile with promising potentials for asthma clinical evaluations and management. Further and larger investigations will be needed to confirm the potential role of microRNA as a clinical marker of bronchial asthma and eventually of pharmacological treatment response.

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“…Notable, many circRNAs could serve as a sponge of miR-34a-5p, including circOgdh (also named mmu_circ_0000231) 176 , circMED12L 180 , circ_FURIN 181 , circ_CSNK1E 182 , circ0036602 183 , circ-LRP1B 184 , circHUWE1 185 , circITGA7 186 , circNFIX 187 , 188 , circRNA-CIDN 189 , circ_0009910 190 , circ_0039569 191 , hsa_circ_0018069 192 , suggesting that these circRNAs may promote lipid synthesis but suppress lipid accumulation by regulating miR-34a-5p/ACSL, ATGL, and ADAM10 axis.…”

Section: The Potential Role and Mechanism Of The Circrna/mirna Axis I...mentioning

confidence: 99%

The potential role and mechanism of circRNA/miRNA axis in cholesterol synthesis

Chen¹,

Xu²,

Wu³

et al. 2023

Int. J. Biol. Sci.

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Cholesterol levels are an initiating risk factor for atherosclerosis. Many genes play a central role in cholesterol synthesis, including HMGCR, SQLE, HMGCS1, FDFT1, LSS, MVK, PMK, MVD, FDPS, CYP51, TM7SF2, LBR, MSMO1, NSDHL, HSD17B7, DHCR24, EBP, SC5D, DHCR7, IDI1/2. Especially, HMGCR, SQLE, FDFT1, LSS, FDPS, CYP51, and EBP are promising therapeutic targets for drug development due to many drugs have been approved and entered into clinical research by targeting these genes. However, new targets and drugs still need to be discovered. Interestingly, many small nucleic acid drugs and vaccines were approved for the market, including Inclisiran, Patisiran, Inotersen, Givosiran, Lumasiran, Nusinersen, Volanesorsen, Eteplirsen, Golodirsen, Viltolarsen, Casimersen, Elasomeran, Tozinameran. However, these agents are all linear RNA agents. Circular RNAs (circRNAs) may have longer half-lives, higher stability, lower immunogenicity, lower production costs, and higher delivery efficiency than these agents due to their covalently closed structures. CircRNA agents are developed by several companies, including Orna Therapeutics, Laronde, and CirCode, Therorna. Many studies have shown that circRNAs regulate cholesterol synthesis by regulating HMGCR, SQLE, HMGCS1, ACS, YWHAG, PTEN, DHCR24, SREBP-2, and PMK expression. MiRNAs are essential for circRNA-mediated cholesterol biosynthesis. Notable, the phase II trial for inhibiting miR-122 with nucleic acid drugs has been completed. Suppressing HMGCR, SQLE, and miR-122 with circRNA_ABCA1, circ-PRKCH, circEZH2, circRNA-SCAP, and circFOXO3 are the promising therapeutic target for drug development, specifically the circFOXO3. This review focuses on the role and mechanism of the circRNA/miRNA axis in cholesterol synthesis in the hope of providing knowledge to identify new targets.

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circ_CSNK1E modulates airway smooth muscle cells proliferation and migration via miR-34a-5p/VAMP2 axis in asthma

Cited by 11 publications

References 26 publications

The Stress-Responsive microRNA-34a Alters Insulin Signaling and Actions in Adipocytes through Induction of the Tyrosine Phosphatase PTP1B

The Stress-Responsive microRNA-34a Alters Insulin Signaling and Actions in Adipocytes through Induction of the Tyrosine Phosphatase PTP1B

Circulating MicroRNAs Expression Profile in Lung Inflammation: A Preliminary Study

The potential role and mechanism of circRNA/miRNA axis in cholesterol synthesis

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