Zhao Xinge, Min Xuejie, Wang Zhenyu, Chen Xiaoxia, Ge Chao, Zhao Fangyu, Tian Hua, Chen Taoyang, Li Jinjun
State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
Department of Oncology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China.
Int J Biol Sci. 2024 Oct 28;20(15):5850-5867. doi: 10.7150/ijbs.95174. eCollection 2024.
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 and 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.
核受体亚家族4 A组成员3（NR4A3）是孤儿核受体超家族的成员，通过与序列特异性DNA结合发挥转录因子活性。鉴于NR4A3在肝细胞癌（HCC）中调节基因转录的具体机制尚未阐明，我们的研究旨在探讨NR4A3在调控靶基因CDKN2AIP（CDKN2A相互作用蛋白）中的转录作用，该靶基因将抑制HCC的发展。我们的数据表明，NR4A3在人类HCC组织中表达下调，且NR4A3低表达与预后不良相关，这表明NR4A3可能在HCC中作为肿瘤抑制基因发挥作用。NR4A3过表达抑制细胞增殖、克隆形成，使细胞周期停滞在G0/G1期并抑制肿瘤生长，并促进DNA损伤。NR4A3可在转录水平直接调控CDKN2AIP的表达，这表明NR4A3可能在HCC中作为转录因子发挥作用，并且可能作为预测HCC患者预后的潜在生物标志物。
