CoChat
Sign Up
Cited by 35Cancer-related molecular mechanisms researchAutophagy in Disease and TherapyRNA Interference and Gene Delivery

LncRNA expression profile during autophagy and Malat1 function in macrophages

Open access
Ma, Zhanbing, Zhang, Jing, Xu, Xiangrong, Qu, Yuliang, Dong, Hui, Dang, Jie, Huo, Zhenghao, Xu, Guangxian·2019·PLOS ONE
DOI 10.1371/journal.pone.0221104PMC PMC6699732
Open this paper in CoChat — free accountOpen PDF

Abstract

Long noncoding RNAs (lncRNAs) are a class of functional non-coding transcripts that are longer than 200 nt and regulate gene expression via diverse mechanisms in eukaryotes. In fact, they have emerged as critical epigenetic and transcriptional regulators of autophagy in mammals in response to various stressors. Autophagy not only plays a crucial role in maintaining cellular homeostasis, but it is also essential to immunity, targets intracellular pathogens for degradation, modulates inflammation, and participates in adaptive immune responses. However, the expression profile of lncRNA and its role in regulating autophagy in macrophages have been poorly defined. Here, we used transcriptomic and bioinformatics to analysis LncRNA expression profile during autophagy and functional studies to evaluate the function of the metastasis-associated lung adenocarcinoma transcript-1 (Malat1) lncRNA in macrophages. A total of 1112 putative lncRNAs (240 novel lncRNAs) were identified, including 831 large intergenic, 129 intronic, and 152 anti-sense lncRNA, of which 59 differentially expressed transcripts exhibited a greater than 1.5-fold change under different conditions. The interaction of Malat1 lncRNA with microRNA (mir)-23-3p and lysosomal-associated membrane protein 1 (Lamp1) was found, Malat1 releases inhibition of Lamp1 expression in macrophages through competitive adsorption of mir-23-3p. The results of this study provide a better understanding of lncRNA function in macrophages and a basis for further investigation into the roles and mechanisms of ncRNA in immunology, particularly the functions of Malat1 and mir-23-3p in the pathogenesis of macrophages.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0221104

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • lncRNA Malat1 competitively adsorbs miR-23-3p to regulate autophagy by releasing LAMP1 expression.

    “Furthermore, long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript-1 (Malat1) associated with metabolism in macrophages competitively adsorbs miR-23–3p to regulate autophagy processes by releasing lysosomal-associated membrane protein 1 (LAMP1) expression [29].”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [29]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 64

  1. [1]Fang S, Zhang L, Guo J, Niu Y, Wu Y, Li H, et al NONCODEV5: a comprehensive annotation database for long non-coding RNAs. Nucleic Acids Res. 2018; 46(D1): D308– d314. 10.1093/nar/gkx1107 29140524 PMC5753287 · DOI
  2. [2]Dykes I, Emanueli C Transcriptional and Post-transcriptional Gene Regulation by Long Non-coding RNA. Genomics Proteomics Bioinformatics. 2017 10.1016/j.gpb.2016.12.005 28529100 PMC5487525 · DOI
  3. [3]Backofen R, Gorodkin J, Hofacker IL, Stadler PF Comparative RNA Genomics. Methods Mol Biol. 2018; 1704: 363– 400. 10.1007/978-1-4939-7463-4_14 29277874 · DOI
  4. [4]Adelman K, Egan E Non-coding RNA: More uses for genomic junk. Nature. 2017; 543(7644): 183– 185. 10.1038/543183a 28277509 · DOI
  5. [5]Elkon R, Agami R Characterization of noncoding regulatory DNA in the human genome. Nat Biotechnol. 2017; 35(8): 732– 746. 10.1038/nbt.3863 28787426 · DOI
  6. [6]Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y, et al The landscape of long noncoding RNAs in the human transcriptome. Nat Genet. 2015; 47(3): 199– 208. 10.1038/ng.3192 25599403 PMC4417758 · DOI · Paper page
  7. [7]Schmitt AM, Garcia JT, Hung T, Flynn RA, Shen Y, Qu K, et al An inducible long noncoding RNA amplifies DNA damage signaling. Nat Genet. 2016; 48(11): 1370– 1376. 10.1038/ng.3673 27668660 PMC5083181 · DOI
  8. [8]Mondal T, Subhash S, Vaid R, Enroth S, Uday S, Reinius B, et al MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures. Nat Commun. 2015; 6: 7743 10.1038/ncomms8743 26205790 PMC4525211 · DOI
  9. [9]Zhang L, Yang Z, Trottier J, Barbier O, Wang L Long noncoding RNA MEG3 induces cholestatic liver injury by interaction with PTBP1 to facilitate shp mRNA decay. Hepatology. 2017; 65(2): 604– 615. 10.1002/hep.28882 27770549 PMC5258819 · DOI
  10. [10]Kallen AN, Zhou XB, Xu J, Qiao C, Ma J, Yan L, et al The imprinted H19 lncRNA antagonizes let-7 microRNAs. Mol Cell. 2013; 52(1): 101– 112. 10.1016/j.molcel.2013.08.027 24055342 PMC3843377 · DOI
  11. [11]Du Z, Sun T, Hacisuleyman E, Fei T, Wang X, Brown M, et al Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer. Nat Commun. 2016; 7: 10982 10.1038/ncomms10982 26975529 PMC4796315 · DOI
  12. [12]Gaiti F, Fernandez-Valverde SL, Nakanishi N, Calcino AD, Yanai I, Tanurdzic M, et al Dynamic and Widespread lncRNA Expression in a Sponge and the Origin of Animal Complexity. Mol Biol Evol. 2015; 32(9): 2367– 2382. 10.1093/molbev/msv117 25976353 PMC4540969 · DOI
  13. [13]Yu X, Zhang Y, Li T, Ma Z, Jia H, Chen Q, et al Long non-coding RNA Linc-RAM enhances myogenic differentiation by interacting with MyoD. Nat Commun. 2017; 8: 14016 10.1038/ncomms14016 28091529 PMC5241866 · DOI
  14. [14]Bernardes de Jesus B, Marinho SP, Barros S, Sousa-Franco A, Alves-Vale C, Carvalho T, et al Silencing of the lncRNA Zeb2-NAT facilitates reprogramming of aged fibroblasts and safeguards stem cell pluripotency. Nat Commun. 2018; 9(1): 94 10.1038/s41467-017-01921-6 29311544 PMC5758807 · DOI
  15. [15]Lu Z, Carter AC, Chang HY Mechanistic insights in X-chromosome inactivation. Philos Trans R Soc Lond, B, Biol Sci. 2017; 372(1733). 10.1098/rstb.2016.0356 28947655 PMC5627158 · DOI
  16. [16]Noack F, Calegari F Epitranscriptomics: A New Regulatory Mechanism of Brain Development and Function. Front Neurosci. 2018; 12: 85 10.3389/fnins.2018.00085 29515357 PMC5826231 · DOI
  17. [17]Schmitt AM, Chang HY Long Noncoding RNAs in Cancer Pathways. Cancer Cell. 2016; 29(4): 452– 463. 10.1016/j.ccell.2016.03.010 27070700 PMC4831138 · DOI
  18. [18]Kugelberg E Antiviral immunity: Linking lncRNA to IFN regulation. Nat Rev Immunol. 2014; 14(12): 779
  19. [19]Atianand MK, Cafferey DR, Fitzgerald KA Immunobiology of Long Noncoding RNAs. Annu Rev Immunol. 2017 10.1146/annurev-immunol-041015-055459 28125358 PMC6449690 · DOI
  20. [20]Highlighting advances in autophagy. Nat Cell Biol. 2018; 20(3): 223 10.1038/s41556-018-0061-z 29476159 · DOI
  21. [21]Kuballa P, Nolte WM, Castoreno AB, Xavier RJ Autophagy and the immune system. Annu Rev Immunol. 2012; 30(611– 646. 10.1146/annurev-immunol-020711-074948 22449030 · DOI
  22. [22]Chen Z, Wang T, Liu Z, Zhang G, Wang J, Feng S, et al Inhibition of Autophagy by MiR-30A Induced by Mycobacteria tuberculosis as a Possible Mechanism of Immune Escape in Human Macrophages. Jpn J Infect Dis. 2015; 68(5): 420– 424. 10.7883/yoken.JJID.2014.466 25866116 · DOI
  23. [23]Zhang J, Wang P, Wan L, Xu S, Pang D The emergence of noncoding RNAs as Heracles in autophagy. Autophagy. 2017; 13(6): 1004– 1024. 10.1080/15548627.2017.1312041 28441084 PMC5486373 · DOI
  24. [24]Frankel LB, Lubas M, Lund AH Emerging connections between RNA and autophagy. Autophagy. 2017; 13(1): 3– 23. 10.1080/15548627.2016.1222992 27715443 PMC5240835 · DOI
  25. [25]Yang L, Wang H, Shen Q, Feng L, Jin H Long non-coding RNAs involved in autophagy regulation. Cell Death Dis. 2017; 8(10): e3073 10.1038/cddis.2017.464 28981093 PMC5680586 · DOI
  26. [26]Thomson DW, Dinger ME Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet. 2016; 17(5): 272– 283. 10.1038/nrg.2016.20 27040487 · DOI · Paper page
  27. [27]Tay Y, Rinn J, Pandolfi PP The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014; 505(7483): 344– 352. 10.1038/nature12986 24429633 PMC4113481 · DOI · Paper page
  28. [28]Wang K, Liu CY, Zhou LY, Wang JX, Wang M, Zhao B, et al APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p. Nat Commun. 2015; 6: 6779 10.1038/ncomms7779 25858075 · DOI · Paper page
  29. [29]Li L, Chen H, Gao Y, Wang YW, Zhang GQ, Pan SH, et al Long noncoding RNA MALAT1 promotes aggressive pancreatic cancer proliferation and metastasis via the stimulation of autophagy. Mol Cancer Ther. 2016 10.1158/1535-7163.MCT-16-0008 27371730 · DOI
  30. [30]Li Z, Li J, Tang N Long noncoding RNA Malat1 is a potent autophagy inducer protecting brain microvascular endothelial cells against oxygen-glucose deprivation/reoxygenation-induced injury by sponging miR-26b and upregulating ULK2 expression. Neuroscience. 2017; 354: 1– 10. 10.1016/j.neuroscience.2017.04.017 28433650 · DOI
  31. [31]Fu Z, Luo W, Wang J, Peng T, Sun G, Shi J, et al Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma. Biochem Biophys Res Commun. 2017; 492(3): 480– 486. 10.1016/j.bbrc.2017.08.070 28834690 · DOI
  32. [32]Cui H, Banerjee S, Guo S, Xie N, Ge J, Jiang D, et al Long noncoding RNA Malat1 regulates differential activation of macrophage and response to lung injury. JCI Insight. 2019 10.1172/jci.insight.124522 30676324 PMC6478413 · DOI
  33. [33]Luo H, Bu D, Sun L, Fang S, Liu Z, Zhao Y Identification and function annotation of long intervening noncoding RNAs. Brief Bioinform. 2017; 18(5): 789– 797. 10.1093/bib/bbw046 27439532 · DOI
  34. [34]Li J, Ma W, Zeng P, Wang J, Geng B, Yang J, et al LncTar: a tool for predicting the RNA targets of long noncoding RNAs. Brief Bioinform. 2015; 16(5): 806– 812. 10.1093/bib/bbu048 25524864 · DOI
  35. [35]Bustin SA, Wittwer CT MIQE: A Step Toward More Robust and Reproducible Quantitative PCR. Clin Chem. 2017; 63(9): 1537– 1538. 10.1373/clinchem.2016.268953 28606913 · DOI
  36. [37]Storey JD, Tibshirani R Statistical significance for genomewide studies. Proc Natl Acad Sci U S A. 2003; 100(16): 9440– 9445. 10.1073/pnas.1530509100 12883005 PMC170937 · DOI · Paper page
  37. [38]YiRen H, YingCong Y, Sunwu Y, Keqin L, Xiaochun T, Senrui C, et al Long noncoding RNA MALAT1 regulates autophagy associated chemoresistance via mir-23-3p sequestration in gastric cancer. Mol Cancer. 2017; 16(1): 174 10.1186/s12943-017-0743-3 29162158 PMC5699172 · DOI
  38. [39]Huang J, Yang Y, Fang F, Liu K MALAT1 modulates the autophagy of retinoblastoma cell through miR-124-mediated stx17 regulation. J Cell Biochem. 2018; 119(5): 3853– 3863. 10.1002/jcb.26464 29073720 · DOI
  39. [40]Guo D, Ma J, Yan L, Li T, Li Z, Han X, et al Down-Regulation of Lncrna MALAT1 Attenuates Neuronal Cell Death Through Suppressing Beclin1-Dependent Autophagy by Regulating Mir-30a in Cerebral Ischemic Stroke. Cell Physiol Biochem. 2017; 43(1): 182– 194. 10.1159/000480337 28854438 · DOI
  40. [41]Alessandrini F, Pezzè L, Ciribilli Y LAMPs: Shedding light on cancer biology. Semin Oncol. 2017; 44(4): 239– 253. 10.1053/j.seminoncol.2017.10.013 29526252 · DOI
  41. [42]Cohen-Dvashi H, Israeli H, Shani O, Katz A, Diskin R Role of LAMP1 Binding and pH Sensing by the Spike Complex of Lassa Virus. J Virol. 2016; 90(22): 10329– 10338. 10.1128/JVI.01624-16 27605678 PMC5105667 · DOI
  42. [43]Cohen-Dvashi H, Cohen N, Israeli H, Diskin R Molecular Mechanism for LAMP1 Recognition by Lassa Virus. J Virol. 2015; 89(15): 7584– 7592. 10.1128/JVI.00651-15 25972533 PMC4505663 · DOI
  43. [44]Redis RS, Calin GA SnapShot: Non-coding RNAs and Metabolism. Cell Metab. 2017; 25(1): 220– 220.e221. 10.1016/j.cmet.2016.12.012 28076764 · DOI
  44. [45]Aredia F, Scovassi AI A new function for miRNAs as regulators of autophagy. Future Med Chem. 2017; 9(1): 25– 36. 10.4155/fmc-2016-0173 27957876 · DOI
  45. [46]Ilott NE, Ponting CP Predicting long non-coding RNAs using RNA sequencing. Methods. 2013; 63(1): 50– 59. 10.1016/j.ymeth.2013.03.019 23541739 · DOI
  46. [47]Uchida S. High-Throughput Methods to Detect Long Non-Coding RNAs. High Throughput. 2017; 6(3). 10.3390/ht6030012 29485610 PMC5734189 · DOI
  47. [48]Hu X, Chen S, Jia C, Xue S, Dou C, Dai Z, et al Gene expression profile and long non-coding RNA analysis, using RNA-Seq, in chicken embryonic fibroblast cells infected by avian leukosis virus J. Arch Virol. 2018; 163(3): 639– 647. 10.1007/s00705-017-3659-8 29198037 · DOI
  48. [49]Golicz AA, Singh MB, Bhalla PL The Long Intergenic Noncoding RNA (LincRNA) Landscape of the Soybean Genome. Plant Physiol. 2018; 176(3): 2133– 2147. 10.1104/pp.17.01657 29284742 PMC5841726 · DOI
  49. [50]Chekanova JA Long non-coding RNAs and their functions in plants. Curr Opin Plant Biol. 2015; 27: 207– 216. 10.1016/j.pbi.2015.08.003 26342908 · DOI
  50. [51]Gao X, Ye J, Yang C, Luo L, Liu Y, Ding J, et al RNA-seq analysis of lncRNA-controlled developmental gene expression during puberty in goat & rat. BMC Genet. 2018; 19(1): 19 10.1186/s12863-018-0608-9 29609543 PMC5879571 · DOI
  51. [52]Mao AP, Shen J, Zuo Z Expression and regulation of long noncoding RNAs in TLR4 signaling in mouse macrophages. BMC Genomics. 2015; 16: 45 10.1186/s12864-015-1270-5 25652569 PMC4320810 · DOI
  52. [53]Pawar K, Hanisch C, Palma Vera SE, Einspanier R, Sharbati S Down regulated lncRNA MEG3 eliminates mycobacteria in macrophages via autophagy. Sci Rep. 2016; 6: 19416 10.1038/srep19416 26757825 PMC4725832 · DOI
  53. [54]Yang X, Yang J, Wang J, Wen Q, Wang H, He J, et al Microarray analysis of long noncoding RNA and mRNA expression profiles in human macrophages infected with Mycobacterium tuberculosis. Sci Rep. 2016; 6(38963 10.1038/srep38963 27966580 PMC5155227 · DOI
  54. [55]Duval M, Cossart P, Lebreton A. Mammalian microRNAs and long noncoding RNAs in the host-bacterial pathogen crosstalk. Semin Cell Dev Biol. 2017; 65: 11– 19. 10.1016/j.semcdb.2016.06.016 27381344 PMC7089780 · DOI
  55. [56]Zur Bruegge J, Einspanier R, Sharbati S A. Long Journey Ahead: Long Non-coding RNAs in Bacterial Infections. Front Cell Infect Microbiol. 2017; 7: 95 10.3389/fcimb.2017.00095 28401065 PMC5368183 · DOI
  56. [57]Kotzin JJ, Mowel WK, Henao-Mejia J. Viruses hijack a host lncRNA to replicate. Science. 2017; 358(6366): 993– 994. 10.1126/science.aar2300 29170219 · DOI
  57. [58]Murphy MB, Medvedev AE. Long noncoding RNAs as regulators of Toll-like receptor signaling and innate immunity. J Leukoc Biol. 2016; 99(6): 839– 850. 10.1189/jlb.2RU1215-575R 26965636 PMC6608019 · DOI
  58. [59]Eissmann M, Gutschner T, Hammerle M, Gunther S, Caudron-Herger M, Gross M, et al Loss of the abundant nuclear non-coding RNA MALAT1 is compatible with life and development. RNA Biol. 2012; 9(8): 1076– 1087. 10.4161/rna.21089 22858678 PMC3551862 · DOI
  59. [60]Ma XY, Wang JH, Wang JL, Ma CX, Wang XC, Liu FS, et al Malat1 as an evolutionarily conserved lncRNA, plays a positive role in regulating proliferation and maintaining undifferentiated status of early-stage hematopoietic cells. BMC Genomics. 2015; 16: 676 10.1186/s12864-015-1881-x 26335021 PMC4559210 · DOI
  60. [61]Sun Q, Hao Q, Prasanth KV. Nuclear Long Noncoding RNAs: Key Regulators of Gene Expression. Trends Genet. 2017 10.1016/j.tig.2017.11.005 29249332 PMC6002860 · DOI
  61. [62]Zhou HJ, Wang LQ, Wang DB, Yu JB, Zhu Y, Xu QS, et al Long non-coding RNA MALAT1 contributes to inflammatory response of microglia following spinal cord injury via modulating miR-199b/IKKbeta/NF-kappaB signaling pathway. Am J Physiol Cell Physiol. 2018 10.1152/ajpcell.00278.2017 29631367 · DOI
  62. [63]Yan W, Wu Q, Yao W, Li Y, Liu Y, Yuan J, et al MiR-503 modulates epithelial-mesenchymal transition in silica-induced pulmonary fibrosis by targeting PI3K p85 and is sponged by lncRNA MALAT1. Sci Rep. 2017; 7(1): 11313 10.1038/s41598-017-11904-8 28900284 PMC5596016 · DOI
  63. [64]An Y, Zhang Z, Shang Y, Jiang X, Dong J, Yu P, et al mir-23-3p regulates the chemoresistance of gastric cancer cells by targeting ATG12 and HMGB2. Cell Death Dis. 2015; 6: e1766 10.1038/cddis.2015.123 25996293 PMC4669702 · DOI · Paper page
  64. [65]Li S, Pan X, Yang S, Ma A, Yin S, Dong Y, et.al LncRNA MALAT1 promotes autophagy in HUVECs by inhibiting the PI3K/AKT pathway. J Cell Biochem. 2019 3; 120(3): 4092– 4101. 10.1002/jcb.27694 30485490 · DOI

Cited by

Sorted by citations

Authors
Ma, Z., Zhang, J., Xu, X., Qu, Y., Dong, H., Dang, J., Huo, Z., & Xu, G.
Affiliations
Ningxia Medical University (CN)
Corresponding author
  • Huo, Zhenghao
  • Xu, Guangxian
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2019-08-19
Volume
14
Issue
8
Pages
e0221104
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0221104
PMC
PMC6699732
OpenAlex
W2969961864
Cited by
35
References
1
Citations by year
2025: 1 · 2024: 6 · 2023: 7 · 2022: 7 · 2021: 8 · 2020: 6
FWCI
2.53
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Natural Science Foundation of China (81860355)
  • Ningxia Scientific and technological innovation leader training project (KJT2015020)
  • First-class Discipline construction of clinical medicine of Ningxia Medical University (NXYLXUK2017A05)
  • Natural Science Foundation of Ningxia Province of China (2018AAC03088)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
long non-coding RNA, MALAT1, autophagy, macrophages, lncRNA expression profiles, LAMP1, microRNA competition, novel lncRNAs, intergenic lncRNAs, intronic lncRNAs, immune regulation
MeSH terms
RAW 264.7 Cells, RNA-Seq, Animals, Autophagy, Computational Biology, MicroRNAs, Mice, Lysosomal Membrane Proteins, Lysosomal-Associated Membrane Protein 1, RNA, Long Noncoding

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review