c-Myc affects hedgehog pathway via KCNQ1OT1/RAC1: A new mechanism for regulating HSC proliferation and epithelial-mesenchymal transition.
Dig Liver Dis
; 53(11): 1458-1467, 2021 Nov.
Article
in En
| MEDLINE
| ID: mdl-33451909
ABSTRACT
BACKGROUND:
This study aimed to probe into the potential mechanism of KCNQ1OT1 in liver fibrosis.METHODS:
The pathological changes in liver tissues were observed by Masson and hematoxylin-eosin (HE) staining. The proliferation or cell cycle of hepatic stellate cells (HSCs) was analyzed by MTT or flow cytometry. The expressions of epithelial markers E-cadherin, interstitial markers Snail and Vimentin, and hedgehog signaling pathway-related molecules Hhip, Shh, and Gli2 were detected by Western blot. The interaction or binding of c-Myc with the KCNQ1OT1 promoter was analyzed by dual-luciferase reporter gene or Chromatin immunoprecipitation (ChIP)-qPCR, and the interaction between KCNQ1OT1 and RAC1 was assessed by RNA immunoprecipitation and RNA pull-down. Moreover, the stability of RAC1 protein was detected by cycloheximide-chase and ubiquitination.RESULTS:
c-Myc and KCNQ1OT1 were up-regulated in liver fibrosis tissues and cells. After the interference with c-Myc in primary-1-Day HSCs, the down-regulated KCNQ1OT1 restrained HSC proliferation and EMT by down-regulating RAC1 expression and restraining the hedgehog pathway.CONCLUSION:
Our results indicated that the interference with c-Myc down-regulated RAC1 expression and restrained the hedgehog pathway by down-regulating KCNQ1OT1, thus restraining HSC proliferation and EMT in liver fibrosis.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hepatic Stellate Cells
/
Epithelial-Mesenchymal Transition
/
RNA, Long Noncoding
/
Liver Cirrhosis
Limits:
Animals
/
Humans
Language:
En
Journal:
Dig Liver Dis
Journal subject:
GASTROENTEROLOGIA
Year:
2021
Document type:
Article