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Propofol Ameliorates the Proliferation and Epithelial-Mesenchymal Transition of Hepatoma Carcinoma Cells via Non-Coding RNA Activated by DNA Damage (NORAD)/microRNA (miR)-556-3p/Migration and Invasion Enhancer 1 (MIEN1) Axis.

Abstract
Propofol has been previously demonstrated to relieve hepatocellular carcinoma (HCC). However, the specific molecular mechanisms mediated by propofol remain to be explored. mRNA or miRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Protein expression was determined by Western blot. The interaction between microRNA (miR)-556-3p and long coding RNA non-coding RNA activated by DNA damage (NORAD) or migration and invasion enhancer 1 (MIEN1) was verified by luciferase reporter gene and RNA pull-down assays. Cellular functions were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetra-zolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), and Transwell assays. Propofol notably suppressed the proliferation and EMT of Hep3B and SNU449 cell lines. NORAD was overexpressed in the HCC tissues and cells, while propofol decreased NORAD levels in the HCC cells. Conversely, overexpression of NORAD partially restored malignant behaviors of the HCC cells and abolished the effects of propofol. Additionally, NORAD sponged miR-556-3p to upregulate MIEN1. However, the knockdown of MIEN1 suppressed the proliferation and EMT of HCC cells. Propofol inhibited HCC cell proliferation and EMT progress via NORAD/miR-556-3p/MIEN1 axis. These data provided a potent prognosis and diagnostic marker for HCC and supplemented the underlying mechanism of propofol-induced anti-tumor effects.
AuthorsYanna Liu, Xiang Wang, Hongyu Li, Enjian Guan, Kaidi Luo
JournalJournal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer (J Environ Pathol Toxicol Oncol) Vol. 40 Issue 4 Pg. 87-97 ( 2021) ISSN: 2162-6537 [Electronic] United States
PMID34936303 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents
  • Intracellular Signaling Peptides and Proteins
  • MIEN1 protein, human
  • MIRN556 microRNA, human
  • MicroRNAs
  • NORAD long non-coding RNA, human
  • Neoplasm Proteins
  • RNA, Long Noncoding
  • Propofol
Topics
  • Antineoplastic Agents (pharmacology)
  • Carcinoma, Hepatocellular (drug therapy)
  • Cell Proliferation (drug effects)
  • DNA Damage (drug effects)
  • Epithelial-Mesenchymal Transition (drug effects)
  • Humans
  • Intracellular Signaling Peptides and Proteins (genetics, metabolism)
  • Liver Neoplasms (drug therapy)
  • MicroRNAs (genetics, metabolism)
  • Neoplasm Proteins (genetics, metabolism)
  • Propofol (pharmacology)
  • RNA, Long Noncoding (genetics, metabolism)

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