Advertisement

Blocking SNHG14 Antagonizes Lipopolysaccharides-Induced Acute Lung Injury via SNHG14/miR-124-3p Axis

Published:February 27, 2021DOI:https://doi.org/10.1016/j.jss.2020.10.034

      Highlights:

      • SNHG14 was upregulated, and miR-124-3p was downregulated by LPS in human lung epithelial cells in vitro.
      • Silencing of SNHG14 and overexpression of miR-124-3p could attenuate LPS-induced apoptosis and inflammation in A549 cells.
      • miR-124-3p, sponged by SNHG14, negatively regulated TGFBR2 expression via target binding.
      • There was a novel SNHG14/miR-124-3p/TGFBR2 circuit in ALI.

      Abstract

      Background

      Emerging evidence show that long noncoding RNAs (lncRNAs) are crucial regulators in pathophysiology of acute lung injury (ALI). Small nucleolar RNA host gene 14 (SNHG14) is a novel oncogenic lncRNA, and has been associated with inflammation-related cell injuries. Thus, we wondered the role and mechanism of SNHG14 in lipopolysaccharides (LPS)-induced ALI cell model.

      Methods

      Expression of SNHG14, miRNA (miR)-124-3p, and transforming growth factor β type 2 receptor (TGFBR2) was detected by RT-qPCR and western blotting. Cell apoptosis was determined by methyl thiazolyl tetrazolium assay, flow cytometry, western blotting, and lactate dehydrogenase activity kit. Inflammation was measured by enzyme-linked immunosorbent assay. The interaction among SNHG14, miR-124-3p, and TGFBR2 was validated by dual-luciferase reporter assay and RNA immunoprecipitation.

      Results

      LPS administration attenuated human lung epithelial cell viability and B-cell lymphoma-2 expression, but augmented apoptosis rate, cleaved-caspase-3 expression, lactate dehydrogenase activity, and secretions of tumor necrosis factor-α, interleukin-1β, and IL-6 in A549 cells. Thus, LPS induced A549 cells apoptosis and inflammation, wherein SNHG14 was upregulated and miR-124-3p was downregulated. However, silencing SNHG14 could suppress LPS-induced apoptosis and inflammation depending on upregulating miR-124-3p via target binding. Similarly, overexpressing miR-124-3p attenuated LPS-induced A549 cells injury through inhibiting its downstream target TGFBR2. Furthermore, SNHG14 knockdown could also affect TGFBR2 expression via miR-124-3p.

      Conclusions

      SNHG14 knockdown prevents A549 cells from LPS-induced apoptosis and inflammation through regulating miR-124-3p and TGFBR2, suggesting a novel SNHG14/miR-124-3p/TGFBR2 circuit in alveolar epithelial cells on the set of ALI.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Surgical Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Butt Y.
        • Kurdowska A.
        • Allen T.C.
        Acute lung injury: a clinical and molecular review.
        Arch Pathol Lab Med. 2016; 140: 345-350
        • Maca J.
        • Jor O.
        • Holub M.
        • et al.
        Past and present ARDS mortality rates: a systematic review.
        Respir Care. 2017; 62: 113-122
        • Tunceroglu H.
        • Shah A.
        • Porhomayon J.
        • Nader N.D.
        Biomarkers of lung injury in critical care medicine: past, present, and future.
        Immunol Invest. 2013; 42: 247-261
        • Lee H.
        • Abston E.
        • Zhang D.
        • Rai A.
        • Jin Y.
        Extracellular vesicle: an emerging mediator of intercellular crosstalk in lung inflammation and injury.
        Front Immunol. 2018; 9: 924
        • Jin W.
        • Dong C.
        IL-17 cytokines in immunity and inflammation.
        Emerg Microbes Infect. 2013; 2: e60
        • Whitsett J.A.
        • Alenghat T.
        Respiratory epithelial cells orchestrate pulmonary innate immunity.
        Nat Immunol. 2015; 16: 27-35
        • Sweeney R.M.
        • Griffiths M.
        • McAuley D.
        Treatment of acute lung injury: current and emerging pharmacological therapies.
        Semin Respir Crit Care Med. 2013; 34: 487-498
        • Garcia-Laorden M.I.
        • Lorente J.A.
        • Flores C.
        • Slutsky A.S.
        • Villar J.
        Biomarkers for the acute respiratory distress syndrome: how to make the diagnosis more precise.
        Ann Transl Med. 2017; 5: 283
        • Perl M.
        • Lomas-Neira J.
        • Chung C.S.
        • Ayala A.
        Epithelial cell apoptosis and neutrophil recruitment in acute lung injury-a unifying hypothesis? What we have learned from small interfering RNAs.
        Mol Med. 2008; 14: 465-475
        • Ferruelo A.
        • Penuelas O.
        • Lorente J.A.
        MicroRNAs as biomarkers of acute lung injury.
        Ann Transl Med. 2018; 6: 34
        • Zhou T.
        • Garcia J.G.
        • Zhang W.
        Integrating microRNAs into a system biology approach to acute lung injury.
        Transl Res. 2011; 157: 180-190
        • Rajasekaran S.
        • Pattarayan D.
        • Rajaguru P.
        • Sudhakar Gandhi P.S.
        • Thimmulappa R.K.
        MicroRNA regulation of acute lung injury and acute respiratory distress syndrome.
        J Cell Physiol. 2016; 231: 2097-2106
        • Angulo M.
        • Lecuona E.
        • Sznajder J.I.
        Role of MicroRNAs in lung disease.
        Arch Bronconeumol. 2012; 48: 325-330
        • Ma C.
        • Li Y.
        • Zeng J.
        • Wu X.
        • Liu X.
        • Wang Y.
        Mycobacterium bovis BCG triggered MyD88 induces miR-124 feedback negatively regulates immune response in alveolar epithelial cells.
        PLoS One. 2014; 9: e92419
        • Wang Y.
        • Huang C.
        • Chintagari N.R.
        • Xi D.
        • Weng T.
        • Liu L.
        miR-124 regulates fetal pulmonary epithelial cell maturation.
        Am J Physiol Lung Cell Mol Physiol. 2015; 309: L400-L413
        • Wang K.C.
        • Chang H.Y.
        Molecular mechanisms of long noncoding RNAs.
        Mol Cell. 2011; 43: 904-914
        • Zhang Z.
        • Wang Y.
        • Zhang W.
        • Li J.
        • Liu W.
        • Lu W.
        Long non-coding RNA SNHG14 exerts oncogenic functions in non-small cell lung cancer through acting as an miR-340 sponge.
        Biosci Rep. 2019; 39 (BSR20180941)
        • Zhong Y.
        • Yu C.
        • Qin W.
        LncRNA SNHG14 promotes inflammatory response induced by cerebral ischemia/reperfusion injury through regulating miR-136-5p/ROCK1.
        Cancer Gene Ther. 2019; 26: 234-247
        • Tam C.
        • Wong J.H.
        • Tsui S.K.W.
        • Zuo T.
        • Chan T.F.
        • Ng T.B.
        LncRNAs with miRNAs in regulation of gastric, liver, and colorectal cancers: updates in recent years.
        Appl Microbiol Biotechnol. 2019; 103: 4649-4677
        • Nova Z.
        • Skovierova H.
        • Calkovska A.
        Alveolar-capillary membrane-related pulmonary cells as a target in endotoxin-induced acute lung injury.
        Int J Mol Sci. 2019; 20: 831
        • Pittet J.F.
        • Griffiths M.J.
        • Geiser T.
        • et al.
        TGF-beta is a critical mediator of acute lung injury.
        J Clin Invest. 2001; 107: 1537-1544
        • Sureshbabu A.
        • Syed M.A.
        • Boddupalli C.S.
        • et al.
        Conditional overexpression of TGFbeta1 promotes pulmonary inflammation, apoptosis and mortality via TGFbetaR2 in the developing mouse lung.
        Respir Res. 2015; 16: 4
        • Rabbani Z.N.
        • Anscher M.S.
        • Zhang X.
        • et al.
        Soluble TGFbeta type II receptor gene therapy ameliorates acute radiation-induced pulmonary injury in rats.
        Int J Radiat Oncol Biol Phys. 2003; 57: 563-572
        • Cao X.
        • Zhang C.
        • Zhang X.
        • Chen Y.
        • Zhang H.
        MiR-145 negatively regulates TGFBR2 signaling responsible for sepsis-induced acute lung injury.
        Biomed Pharmacother. 2019; 111: 852-858
        • Wang D.
        • Gu C.
        • Liu M.
        • Liu G.
        • Liu H.
        • Wang Y.
        Analysis of long noncoding RNA expression profile in human pulmonary Microvascular endothelial cells exposed to lipopolysaccharide.
        Cell Physiol Biochem. 2019; 52: 653-667
        • Li H.
        • Shi H.
        • Gao M.
        • Ma N.
        • Sun R.
        Long non-coding RNA CASC2 improved acute lung injury by regulating miR-144-3p/AQP1 axis to reduce lung epithelial cell apoptosis.
        Cell Biosci. 2018; 8: 15
        • Wang J.
        • Shen Y.C.
        • Chen Z.N.
        • et al.
        Microarray profiling of lung long non-coding RNAs and mRNAs in lipopolysaccharide-induced acute lung injury mouse model.
        Biosci Rep. 2019; 39 (BSR20181634)
        • Li X.
        • Zhang Q.
        • Yang Z.
        Silence of MEG3 intensifies lipopolysaccharide-stimulated damage of human lung cells through modulating miR-4262.
        Artif Cells Nanomed Biotechnol. 2019; 47: 2369-2378
        • Dai L.
        • Zhang G.
        • Cheng Z.
        • et al.
        Knockdown of LncRNA MALAT1 contributes to the suppression of inflammatory responses by up-regulating miR-146a in LPS-induced acute lung injury.
        Connect Tissue Res. 2018; 59: 581-592
        • Zhang D.
        • Lee H.
        • Haspel J.A.
        • Jin Y.
        Long noncoding RNA FOXD3-AS1 regulates oxidative stress-induced apoptosis via sponging microRNA-150.
        FASEB J. 2017; 31: 4472-4481
        • Wu K.
        • Li J.
        • Qi Y.
        • et al.
        SNHG14 confers gefitinib resistance in non-small cell lung cancer by up-regulating ABCB1 via sponging miR-206-3p.
        Biomed Pharmacother. 2019; 116: 108995
        • Jiao P.
        • Hou J.
        • Yao M.
        • Wu J.
        • Ren G.
        SNHG14 silencing suppresses the progression and promotes cisplatin sensitivity in non-small cell lung cancer.
        Biomed Pharmacother. 2019; 117: 109164
        • Zhu J.
        • Bai J.
        • Wang S.
        • Dong H.
        Down-regulation of long non-coding RNA SNHG14 protects against acute lung injury induced by lipopolysaccharide through microRNA-34c-3p-dependent inhibition of WISP1.
        Respir Res. 2019; 20: 233
        • Pan W.
        • Wei N.
        • Xu W.
        • Wang G.
        • Gong F.
        • Li N.
        MicroRNA-124 alleviates the lung injury in mice with septic shock through inhibiting the activation of the MAPK signaling pathway by downregulating MAPK14.
        Int Immunopharmacol. 2019; 76: 105835
        • Li Q.C.
        • Liang Y.
        • Su Z.B.
        Prophylactic treatment with MSC-derived exosomes attenuates traumatic acute lung injury in rats.
        Am J Physiol Lung Cell Mol Physiol. 2019; 316: L1107-L1117
        • Gu W.
        • Yao L.
        • Li L.
        • et al.
        ICAM-1 regulates macrophage polarization by suppressing MCP-1 expression via miR-124 upregulation.
        Oncotarget. 2017; 8: 111882-111901