Your browser doesn't support javascript.
loading
HuR facilitates miR-93-5p-induced activation of MAP3K2 translation via MAP3K2 3'UTR ARE2 in hepatocellular carcinoma.
Shi, Xuan; Qi, Zhuoran; Huang, Dongbo; Zhu, Jimin; Shen, Xizhong; Liu, Taotao.
Afiliación
  • Shi X; Department of Gastroenterology and Hepatology, and Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032, China.
  • Qi Z; Department of Gastroenterology and Hepatology, and Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032, China.
  • Huang D; Department of Gastroenterology and Hepatology, and Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032, China.
  • Zhu J; Department of Gastroenterology and Hepatology, and Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032, China.
  • Shen X; Department of Gastroenterology and Hepatology, and Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032, China.
  • Liu T; Department of Gastroenterology and Hepatology, and Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032, China; Department of Gastroenterology and Hepatology, Shanghai Geriatric Medical Center, 2560 Chunshen Rd., Shanghai, 201104, China. Ele
Biochem Biophys Res Commun ; 722: 150152, 2024 08 30.
Article en En | MEDLINE | ID: mdl-38795452
ABSTRACT
MicroRNAs (miRNAs) can positively regulate gene expression through an unconventional RNA activation mechanism involving direct targeting 3' untranslated regions (UTRs). Our prior study found miR-93-5p activates mitogen-activated protein kinase kinase kinase 2 (MAP3K2) in hepatocellular carcinoma (HCC) via its 3'UTR. However, the underlying mechanism remains elusive. Here, we identified two candidate AU-rich element (ARE) motifs (ARE1 and ARE2) adjacent to the miR-93-5p binding site located within the MAP3K2 3'UTR using AREsite2. Luciferase reporter and translation assays validated that only ARE2 participated in MAP3K2 activation. Integrative analysis revealed that human antigen R (HuR), an ARE2-associated RNA-binding protein (RBP), physically and functionally interacted with the MAP3K2 3'UTR. Consequently, an HuR-ARE2 complex was shown to facilitate miR-93-5p-mediated upregulation of MAP3K2 expression. Furthermore, bioinformatics analysis and studies of HCC cells and specimens highlighted an oncogenic role for HuR and positive HuR-MAP3K2 expression correlation. HuR is also an enhancing factor in the positive feedback circuit comprising miR-93-5p, MAP3K2, and c-Jun demonstrated in our prior study. The newly identified HuR-ARE2 involvement enriches the mechanism of miR-93-5p-driven MAP3K2 activation and suggests new therapeutic strategies warranted for exploration in HCC.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Carcinoma Hepatocelular / Regiones no Traducidas 3' / MicroARNs / MAP Quinasa Quinasa Quinasa 2 / Proteína 1 Similar a ELAV / Neoplasias Hepáticas Límite: Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Carcinoma Hepatocelular / Regiones no Traducidas 3' / MicroARNs / MAP Quinasa Quinasa Quinasa 2 / Proteína 1 Similar a ELAV / Neoplasias Hepáticas Límite: Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos