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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 41 Issue 4
Apr.  2025
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Article Navigation >  Journal of Clinical Hepatology  > 2025  >  41(4): 690-697

Mechanism of action of Homebox A6 in regulating the proliferation， invasion， metastasis， and apoptosis of HepG2 hepatoma cells

DOI: 10.12449/JCH250414
  • 1.

    Institute of Hepatology，Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 201203，China

  • 2.

    Department of Emergency，Shanghai Traditional Chinese Medicine Hospital，Shanghai University of Traditional Chinese Medicine，Shanghai 200071，China

Research funding:

General Projects of the National Natural Science Foundation of China (82374189);

General Projects of the National Natural Science Foundation of China (81774098)

More Information
  • Corresponding author: CHENG Yang， drchengyang@126.com （ORCID： 0009-0000-2266-5757）
  • Received Date: 2024-08-08
  • Accepted Date: 2024-09-23
  • Published Date: 2025-04-25
    Abstract
  •   Objective  To investigate the effect of Homebox A6 （HOXA6） on the proliferation， invasion， metastasis， and apoptosis of HepG2 hepatoma cells and its association with the PI3K/AKT signaling pathway.  Methods  HepG2 hepatoma cells were cultured， and HOXA6 overexpression plasmid and siRNA were constructed and transfected into cells. The cells were randomly divided into empty plasmid group， HOXA 6 overexpression group， siRNA negative control group， and siRNA HOXA6 interference group. CCK8 assay was used to measure cell proliferation， Transwell assay was used to observe cell invasion， and wound healing assay was used to observe cell migration （related proteins TIMP3， MMP9， and MMP3）. Flow cytometry was used to measure cell apoptosis （related proteins BAX and BCL2）， the BCA method was used to measure protein concentration， and Western Blot was used to measure the expression of related proteins. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the SNK-q test was used for further comparison between two groups.  Results  Compared with the empty plasmid group， HOXA6 overexpression significantly promoted the proliferation， invasion， and migration of HepG2 hepatoma cells （all P<0.001）， and there was a significant reduction in the protein expression of TIMP3 （P<0.001）， while there were significant increases in the expression levels of MMP9 and MMP3 （both P<0.001）. Compared with the siRNA negative control group， HOXA6 interference significantly inhibited the proliferation， invasion， and migration of HepG2 hepatoma cells （all P<0.001）， and there was a significant increase in the protein expression of TIMP3 （P<0.001）， while there were significant reductions in the expression levels of MMP9 and MMP3 （both P<0.001）. Flow cytometry showed that compared with the empty plasmid group， HOXA6 overexpression inhibited the apoptosis of HepG2 hepatoma cells （P<0.001）， with a significant reduction in the expression of the apoptosis-related protein BAX and a significant increase in the expression of BCL2 （both P<0.001）. Compared with siRNA negative control group， HOXA6 interference promoted the apoptosis of HepG2 hepatoma cells （P<0.001）， with a significant increase in the expression of BAX and a significant reduction in the expression of BCL2 （both P<0.001）. Compared with the empty plasmid group， the HOXA6 overexpression group had significantly higher ratios of p-AKT/AKT and p-PI3K/PI3K （both P<0.001）， and compared with the siRNA negative control group， the siRNA HOXA6 interference group had significantly lower ratios of p-AKT/AKT and p-PI3K/PI3K （both P<0.001）.  Conclusion  HOXA6 can promote the proliferation， invasion， and metastasis of HepG2 hepatoma cells and inhibit their apoptosis by activating the PI3K/AKT signaling pathway through phosphorylation.

     

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