Display options
Cite
Masyuk T, Masyuk A, Trussoni C, et al. Autophagy-mediated reduction of miR-345 contributes to hepatic cystogenesis in polycystic liver disease. JHEP Rep. 2021;3(5):100345doi: 10.1016/j.jhepr.2021.100345.
Masyuk, T., Masyuk, A., Trussoni, C., Howard, B., Ding, J., Huang, B., & LaRusso, N. (2021). Autophagy-mediated reduction of miR-345 contributes to hepatic cystogenesis in polycystic liver disease. JHEP reports : innovation in hepatology, 3(5), 100345. https://doi.org/10.1016/j.jhepr.2021.100345
Masyuk, Tatyana, et al. "Autophagy-mediated reduction of miR-345 contributes to hepatic cystogenesis in polycystic liver disease." JHEP reports : innovation in hepatology vol. 3,5 (2021): 100345. doi: https://doi.org/10.1016/j.jhepr.2021.100345
Masyuk T, Masyuk A, Trussoni C, Howard B, Ding J, Huang B, LaRusso N. Autophagy-mediated reduction of miR-345 contributes to hepatic cystogenesis in polycystic liver disease. JHEP Rep. 2021 Aug 05;3(5):100345. doi: 10.1016/j.jhepr.2021.100345. eCollection 2021 Oct. PMID: 34568801; PMCID: PMC8449272.
Copy Download .nbib Format: NLM
Share it on

JHEP Rep. 2021 Aug 05;3(5):100345. doi: 10.1016/j.jhepr.2021.100345. eCollection 2021 Oct.

Autophagy-mediated reduction of miR-345 contributes to hepatic cystogenesis in polycystic liver disease.

JHEP reports : innovation in hepatology

Tatyana Masyuk, Anatoliy Masyuk, Christy Trussoni, Brynn Howard, Jingyi Ding, Bing Huang, Nicholas LaRusso

Affiliations

  1. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.

PMID: 34568801 PMCID: PMC8449272 DOI: 10.1016/j.jhepr.2021.100345

Abstract

BACKGROUND & AIMS: Polycystic liver disease (PLD) is characterised by increased autophagy and reduced miRNA levels in cholangiocytes. Given that autophagy has been implicated in miRNA regulation, we tested the hypothesis that increased autophagy accounts for miRNA reduction in PLD cholangiocytes (PLDCs) and accelerated hepatic cystogenesis.

METHODS: We assessed miRNA levels in cultured normal human cholangiocytes (NHCs), PLDCs, and isolated PLDC autophagosomes by miRNA-sequencing (miRNA-seq), and miRNA targets by mRNA-seq. Levels of miR-345 and miR-345-targeted proteins in livers of animals and humans with PLD, in NHCs and PLDCs, and in PLDCs transfected with pre-miR-345 were assessed by

RESULTS: In total, 81% of miRNAs were decreased in PLDCs, with levels of 10 miRNAs reduced by more than 10 times; miR-345 was the most-reduced miRNA.

CONCLUSION: Autophagy-mediated reduction of miR-345 in PLDCs (

LAY SUMMARY: Polycystic liver disease (PLD) is an incurable genetic disorder characterised by the progressive growth of hepatic cysts. We found that hepatic cystogenesis is increased when the levels of miR-345 in PLD cholangiocytes (PLDCs) are reduced by autophagy. Restoration of miR-345 in PLDCs via inhibition of autophagy decreases hepatic cystogenesis and thus, is beneficial for PLD.

© 2021 The Author(s).

Keywords: ADPKD, autosomal dominant polycystic kidney disease; ADPLD, autosomal dominant polycystic liver disease; AGO2, Argonaute 2; ALG8, alpha-1,3-glucosyltransferase; ALG9, alpha-1,2-mannosyltransferase; ARPKD, autosomal recessive polycystic kidney disease; CDC25A, cell division cycle 25A; CDK6, cyclin-dependent kinase 6; Cell cycle-related proteins; Cholangiocyte proliferation; Cholangiocytes; DNAJB11, DnaJ heat shock protein family (Hsp40) member B11; DZIP1L, DAZ interacting zinc finger protein 1 like; FDR, false discovery rate; GANAB, glucosidase II alpha subunit; GO, Gene Ontology; Genetic liver diseases; HCQ, hydroxychloroquine; ISH, in situ hybridisation; KEGG, Kyoto Encyclopedia of Genes and Genomes; LRP5, low-density lipoprotein receptor-related protein 5; NHC, normal human cholangiocyte; NRC, normal rat cholangiocyte; PCK, polycystic kidney; PCKC, polycystic kidney rat cholangiocyte; PCNA, proliferating cell nuclear antigen; PKD1/2, polycystic kidney disease 1/2; PKHD1, polycystic kidney and hepatic disease 1; PLD treatment; PLD, polycystic liver disease; PLDC, polycystic liver disease cholangiocyte; PRKCSH, protein kinase C substrate 80K-H; RPM, reads per million; SEC61B, SEC61 translocon subunit beta; SEC63, SEC63 homolog, protein translocation regulator; WT, wild type; mTOR, mammalian target of rapamycin; miRISC, RNA-induced silencing complex; miRNA-seq, miRNA-sequencing; snRNA, small nuclear RNA

Conflict of interest statement

The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.

References

  1. Curr Opin Gastroenterol. 2009 May;25(3):265-71 - PubMed
  2. Am J Pathol. 2014 Jan;184(1):110-21 - PubMed
  3. Medicine (Baltimore). 2018 Nov;97(46):e12912 - PubMed
  4. Gastroenterology. 2011 Jun;140(7):1855-9, 1859.e1 - PubMed
  5. Carcinogenesis. 2011 Aug;32(8):1207-15 - PubMed
  6. Curr Drug Targets. 2017;18(8):950-957 - PubMed
  7. FEBS Open Bio. 2018 Apr 24;8(5):860-867 - PubMed
  8. Hepatology. 2018 Jun;67(6):2462-2464 - PubMed
  9. EMBO Rep. 2013 Jun;14(6):568-76 - PubMed
  10. Cell Rep. 2018 Aug 7;24(6):1397-1406 - PubMed
  11. Hepatology. 2017 Oct;66(4):1197-1218 - PubMed
  12. Nat Protoc. 2010 Jun;5(6):1061-73 - PubMed
  13. Curr Opin Gastroenterol. 2019 Mar;35(2):65-72 - PubMed
  14. Hepatology. 2018 Mar;67(3):1088-1108 - PubMed
  15. Cell Cycle. 2009 May 1;8(9):1324-8 - PubMed
  16. PLoS One. 2019 Nov 22;14(11):e0224071 - PubMed
  17. Microrna. 2017;6(1):2-16 - PubMed
  18. Expert Opin Ther Targets. 2020 Jun;24(6):589-599 - PubMed
  19. BMC Syst Biol. 2011 Apr 25;5:56 - PubMed
  20. J Cancer Res Clin Oncol. 2016 Jan;142(1):213-24 - PubMed
  21. Nat Commun. 2019 Sep 12;10(1):4148 - PubMed
  22. Int J Oncol. 2018 Aug;53(2):771-780 - PubMed
  23. Clin Gastroenterol Hepatol. 2016 Jul;14(7):1031-4 - PubMed
  24. Hepatology. 2013 Jul;58(1):409-21 - PubMed
  25. Nat Cell Biol. 2012 Dec;14(12):1314-21 - PubMed
  26. Cell Mol Life Sci. 2016 Mar;73(5):985-1001 - PubMed
  27. J Hepatol. 2018 Apr;68(4):827-837 - PubMed
  28. J Invest Dermatol. 2019 May;139(5):1073-1081 - PubMed
  29. Hepatology. 2014 Feb;59(2):505-17 - PubMed
  30. Arch Oral Biol. 2020 Aug;116:104732 - PubMed
  31. Bull Cancer. 2021 Mar;108(3):304-322 - PubMed
  32. Adv Drug Deliv Rev. 2019 Apr;144:133-147 - PubMed
  33. Cell Signal. 2020 Jul;71:109548 - PubMed
  34. Biomed Pharmacother. 2019 Mar;111:891-900 - PubMed
  35. Br J Cancer. 2015 Aug 11;113(4):660-8 - PubMed
  36. BMC Genomics. 2014 Jun 03;15:423 - PubMed
  37. J Mol Biol. 2016 May 8;428(9 Pt A):1714-24 - PubMed
  38. Nat Rev Mol Cell Biol. 2017 Sep;18(9):533-547 - PubMed
  39. J Clin Invest. 2008 Nov;118(11):3714-24 - PubMed
  40. J Cancer. 2020 Jan 1;11(4):874-882 - PubMed
  41. Gastroenterology. 2012 Mar;142(3):622-633.e4 - PubMed
  42. Gastroenterology. 2007 Mar;132(3):1104-16 - PubMed

Publication Types