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BCLAF1 promotes cell proliferation, invasion and drug-resistance though targeting lncRNA NEAT1 in hepatocellular carcinoma.

AbstractAIMS:
In the present research, we aimed to investigate the effect of Bcl-2-associated transcription factor 1 (BCLAF1) on hepatocellular carcinoma and further explore the special molecular mechanism.
MAIN METHODS:
The expression of BCLAF1 was analyzed in tumor tissues and different hepatocellular cancer cell lines by real-time RT-PCR and Western blot. Cell proliferation and invasion was explored using MTT and Transwell assay respectively. In addition, luciferase reporter assay was performed to determine the binding activity of BCLAF1 and Nuclear enrichment-rich transcription factor 1 (NEAT1) promoter. Finally, the IC50 for 5-Fluorouracil (5-Fu) was measured by MTT assay, and Western blot was used to determine the expression of P-glycoprotein (P-gp) and multidrug resistance protein1 (MRP1).
KEY FINDING:
The result revealed that BCLAF1 was highly expressed in hepatocellular carcinoma tissues and cells. In addition, BCLAF1-siRNA inhibited the proliferation and invasion of hepatocellular carcinoma cells, and overexpression of BCLAF1 promoted proliferation and invasion. Furthermore, luciferase reporter assay demonstrated that BCLAF1 directly interact with lncNEAT1 promoter and improved NEAT1 expression, and BCLAF1 promoted proliferation and invasion through targeting lncRNA NEAT1. What's more, BCLAF1 promoted 5-Fu resistance and the expression of P-gp and MRP1 in hepatocellular carcinoma cells by targeting NEAT1.
SIGNIFICANCE:
The results of the present study suggested that BCLAF1 might be a new gene related to proliferation and drug-resistance of hepatocellular carcinoma. In the future, the search for a deep and reasonable mechanism for the role of BCLAF1 will help us to understand its function more comprehensively, and finally find a new method for the treatment of human cancer.
AuthorsShao-Jiao Mou, Peng-Fei Yang, Yi-Pin Liu, Ning Xu, Wei-Wei Jiang, Wen-Jing Yue
JournalLife sciences (Life Sci) Vol. 242 Pg. 117177 (Feb 01 2020) ISSN: 1879-0631 [Electronic] Netherlands
PMID31870774 (Publication Type: Journal Article)
CopyrightCopyright © 2019 Elsevier Inc. All rights reserved.
Chemical References
  • BCLAF1 protein, human
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • Repressor Proteins
  • Tumor Suppressor Proteins
Topics
  • Adult
  • Blotting, Western
  • Carcinoma, Hepatocellular (metabolism, pathology)
  • Cell Line, Tumor
  • Cell Proliferation
  • Chromatin Immunoprecipitation
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Liver Neoplasms (metabolism, pathology)
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • RNA, Long Noncoding (metabolism, physiology)
  • Real-Time Polymerase Chain Reaction
  • Repressor Proteins (metabolism, physiology)
  • Tumor Suppressor Proteins (metabolism, physiology)

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