RRC ID 82749
Author Zhao X, Min X, Wang Z, Chen X, Ge C, Zhao F, Tian H, Chen T, Li J.
Title NR4A3 inhibits the tumor progression of hepatocellular carcinoma by inducing cell cycle G0/G1 phase arrest and upregulation of CDKN2AIP expression.
Journal Int J Biol Sci
Abstract Nuclear receptor subfamily 4 group A member 3 (NR4A3) is a member of the orphan nuclear receptor superfamily, and exhibits transcription factor activity by binding to sequence-specific DNA. Considering that the specific mechanism by which NR4A3 regulates gene transcription in HCC (hepatocellular carcinoma) has not yet been elucidated, our study aimed to explore the transcriptional role of NR4A3 in regulating the target gene CDKN2AIP (CDKN2A interacting protein), which will suppress the development of HCC. Our data show that NR4A3 is downregulated in human HCC tissues, and that low expression of NR4A3 is correlated with poor prognosis, indicating that NR4A3 could act as a tumor suppressor gene in HCC. NR4A3 overexpression suppresses cell proliferation, clone formation, cell cycle arrest at G0/G1 phase and tumor growth in vitro and in vivo and promote DNA damage. NR4A3 could directly regulate the expression of CDKN2AIP at the transcriptional level, suggesting that NR4A3 may play a role as a transcription factor in HCC and may serve as a potential biomarker for predicting prognosis for HCC patients.
Volume 20(15)
Pages 5850-5867
Published 2024-1-1
DOI 10.7150/ijbs.95174
PII ijbsv20p5850
PMID 39664575
PMC PMC11628324
MeSH Animals Carcinoma, Hepatocellular* / genetics Carcinoma, Hepatocellular* / metabolism Carcinoma, Hepatocellular* / pathology Cell Line, Tumor Cell Proliferation / genetics DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Female Gene Expression Regulation, Neoplastic Humans Liver Neoplasms* / genetics Liver Neoplasms* / metabolism Liver Neoplasms* / pathology Male Mice Receptors, Steroid / genetics Receptors, Steroid / metabolism Receptors, Thyroid Hormone* / genetics Receptors, Thyroid Hormone* / metabolism Up-Regulation
Resource
Human and Animal Cells HuH-7(RCB1366)