Linc02527 promoted autophagy in Intrahepatic cholestasis of pregnancy

Cell Death Dis. 2018 Sep 24;9(10):979. doi: 10.1038/s41419-018-1013-z.

Abstract

LncRNA plays a crucial role in human disease. However, the expression and function of LncRNA in ICP(Intrahepatic cholestasis of pregnancy) is still not fully elucidated. In this study, we found Linc02527 was increased expression in placenta and serum of ICP patients. Ectopically expression of Linc02527 promoted autophagy and proliferate in HTR8 cells. Silencing Linc02527 suppressed the autophagy and proliferate in HTR8 cells. Mechanically study revealed that Linc02527 regulated the expression of ATG5 and ATG7 by sponging miR-3185. Linc02527 directly binding to YBX1 and activated P21. The growth of C57 mouse was retarded when autophagy was activated. In normal condition, inhibited autophagy using chloroquine did not affect the growth of C57 mouse. However, in the condition of autophagy was activated, inhibited autophagy using chloroquine can improve the growth of C57 mouse. Overall, the results of this study identified Linc02527 as a candidate biomarker in ICP and a potential target for ICP therapy. Chloroquine was a potential drug for ICP therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Autophagy / physiology*
  • Autophagy-Related Protein 5 / metabolism
  • Autophagy-Related Protein 7 / metabolism
  • Biomarkers / metabolism
  • Cell Line
  • Cell Proliferation / physiology
  • Chloroquine / administration & dosage
  • Chloroquine / pharmacology
  • Cholestasis, Intrahepatic / blood*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Female
  • Gene Silencing
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism
  • Models, Animal
  • Placenta / metabolism*
  • Placenta / pathology
  • Pregnancy
  • Pregnancy Complications / blood*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Rats, Sprague-Dawley
  • Y-Box-Binding Protein 1 / metabolism

Substances

  • ATG5 protein, human
  • Autophagy-Related Protein 5
  • Biomarkers
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • MicroRNAs
  • RNA, Long Noncoding
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • Chloroquine
  • ATG7 protein, human
  • Autophagy-Related Protein 7

Supplementary concepts

  • Intrahepatic Cholestasis of Pregnancy