Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jun;102(3):157-162.
doi: 10.1111/iep.12396. Epub 2021 May 15.

Xeroderma Pigmentosum group D suppresses proliferation and promotes apoptosis of HepG2 cells by downregulating ERG expression via the PPARγ pathway

Yue He  1 , Wenqiang Tao  2 , Chao Shang  3 , Chan Qi  4 , Dexiang Ji  1 , Wei Lu  1 , Guoan Chen  1
Affiliations

Xeroderma Pigmentosum group D suppresses proliferation and promotes apoptosis of HepG2 cells by downregulating ERG expression via the PPARγ pathway

Yue He et al. Int J Exp Pathol. 2021 Jun.

Abstract

Xeroderma Pigmentosum group D (XPD) gene has been shown to suppress hepatocellular carcinoma (HCC) progression, but its mechanism remains not fully understood. ETS-related gene (ERG) is generally known as an oncogenic gene. This study aimed to explore whether XPD regulated HCC cell proliferation, apoptosis and cell cycle by inhibiting ERG expression via the PPARγ pathway. The human hepatoma cells (HepG2) were transfected with the XPD overexpression vector (pEGFP-N2/XPD) or empty vector (pEGFP-N2). The PPARγ inhibitor GW9662 was used to determine whether XPD effects were mediated by activation of PPARγ pathway. Cell cycle and apoptosis were ascertained by flow cytometry, and cell viability was measured by MTT assay. Reverse transcription-polymerase chain reaction and Western blot were performed to determine the mRNA and protein levels. Overexpression of XPD significantly enhanced the expression of PPARγ and p-PPARγ, whereas it downregulated that of ERG and cdk7. Furthermore, XPD overexpression notably inhibited proliferation, promoted apoptosis and decreased the percentage of cells in the S + G2 phase of HepG2 cells. However, these effects of XPD overexpression were abrogated by GW9662. Collectively, XPD suppresses proliferation and promotes apoptosis of HepG2 cells by downregulating ERG expression via activation of the PPARγ pathway.

Keywords: ERG; PPARγ; XPD; apoptosis; proliferation.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Successful transfection of XPD overexpression vector. HepG2 cells were transfected with pEGFPN2 (A) and pEGFPN2/XPD (B) by Lipofectamine 2000. GFP fluorescence (green) was observed under a fluorescence microscope
FIGURE 2
FIGURE 2
XPD overexpression decreased ERG and cdk7 mRNA expression by upregulating PPAR. The mRNA levels of XPD, ERG, PPAR and cdk7 in HepG2 cells in each group were determined by RTPCR. (A) Representative electrophoresis gels of RTPCR products and (B) quantitative RTPCR analysis of mRNA levels of genes. a: Blank control group; b: liposome group; c: pEGFPN2 group; d: pEGFPN2/XPD group; e: pEGFPN2/XPD+GW9662 group; f: GW9662 group. M: marker. Data were expressed as the meanSD, n=6;*P<.05 vs pEGFPN2 group. # P<.05 vs pEGFPN2/XPD group; P<.05 vs blank control group
FIGURE 3
FIGURE 3
XPD overexpression decreased ERG and cdk7 protein levels by upregulating PPAR. The protein levels of XPD, ERG, PPAR, pPPAR, and cdk7 in HepG2 cells in each group were determined by Western blot. (A) Representative Western blots and (B) quantitative analysis of protein levels. a: Blank control group; b: liposome group; c: pEGFPN2 group; d: pEGFPN2/XPD group; e: pEGFPN2/XPD+GW9662 group; f: GW9662 group. Data were expressed as the meanSD, n=6;*P<.05 vs pEGFPN2 group. # P<.05 vs pEGFPN2/XPD group; P<.05 vs blank control group
See this image and copyright information in PMC

References

    1. Hartke J, Johnson M, Ghabril M. The diagnosis and treatment of hepatocellular carcinoma. Semin Diagn Pathol. 2017;34(2):153–159.. - PubMed
    1. Khemlina G, Ikeda S, Kurzrock R. The biology of Hepatocellular carcinoma: implications for genomic and immune therapies. Mol Cancer. 2017;16(1):149. - PMC - PubMed
    1. Ogunwobi OO, Harricharran T, Huaman J, et al. Mechanisms of hepatocellular carcinoma progression. World J Gastroenterol. 2019;25(19):2279–2293.. - PMC - PubMed
    1. Sameer AS, Nissar S. XPDThe Lynchpin of NER: Molecule, Gene, Polymorphisms, and Role in Colorectal Carcinogenesis. Front Mol Biosci. 2018;5:23. - PMC - PubMed
    1. Coin F, Marinoni JC, Rodolfo C, Fribourg S, Pedrini AM, Egly JM. Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing interaction between XPD and the p44 subunit of TFIIH. Nat Genet. 1998;20(2):184–188.. - PubMed

Publication types

MeSH terms