TY - JOUR
T1 - SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer
AU - Lachiondo-Ortega, Sofia
AU - Rejano-Gordillo, Claudia M.
AU - Simon, Jorge
AU - Lopitz-Otsoa, Fernando
AU - C. Delgado, Teresa
AU - Mazan-Mamczarz, Krystyna
AU - Goikoetxea-Usandizaga, Naroa
AU - Zapata-Pavas, L. Estefanía
AU - García-del Río, Ana
AU - Guerra, Pietro
AU - Peña-Sanfélix, Patricia
AU - Hermán-Sánchez, Natalia
AU - Al-Abdulla, Ruba
AU - Fernandez-Rodríguez, Carmen
AU - Azkargorta, Mikel
AU - Velázquez-Cruz, Alejandro
AU - Guyon, Joris
AU - Martín, César
AU - Zalamea, Juan Diego
AU - Egia-Mendikute, Leire
AU - Sanz-Parra, Arantza
AU - Serrano-Maciá, Marina
AU - González-Recio, Irene
AU - Gonzalez-Lopez, Monika
AU - Martínez-Cruz, Luis Alfonso
AU - Pontisso, Patrizia
AU - Aransay, Ana M.
AU - Barrio, Rosa
AU - Sutherland, James D.
AU - Abrescia, Nicola G.A.
AU - Elortza, Félix
AU - Lujambio, Amaia
AU - Banales, Jesus M.
AU - Luque, Raúl M.
AU - Gahete, Manuel D.
AU - Palazón, Asís
AU - Avila, Matias A.
AU - Jose, Jose J.
AU - De, Supriyo
AU - Daubon, Thomas
AU - Díaz-Quintana, Antonio
AU - Díaz-Moreno, Irene
AU - Gorospe, Myriam
AU - Rodríguez, Manuel S.
AU - Martínez-Chantar, María Luz
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/3/26
Y1 - 2024/3/26
N2 - The posttranslational modification of proteins critically influences many biological processes and is a key mechanism that regulates the function of the RNA-binding protein Hu antigen R (HuR), a hub in liver cancer. Here, we show that HuR is SUMOylated in the tumor sections of patients with hepatocellular carcinoma in contrast to the surrounding tissue, as well as in human cell line and mouse models of the disease. SUMOylation of HuR promotes major cancer hallmarks, namely proliferation and invasion, whereas the absence of HuR SUMOylation results in a senescent phenotype with dysfunctional mitochondria and endoplasmic reticulum. Mechanistically, SUMOylation induces a structural rearrangement of the RNA recognition motifs that modulates HuR binding affinity to its target RNAs, further modifying the transcriptomic profile toward hepatic tumor progression. Overall, SUMOylation constitutes a mechanism of HuR regulation that could be potentially exploited as a therapeutic strategy for liver cancer.
AB - The posttranslational modification of proteins critically influences many biological processes and is a key mechanism that regulates the function of the RNA-binding protein Hu antigen R (HuR), a hub in liver cancer. Here, we show that HuR is SUMOylated in the tumor sections of patients with hepatocellular carcinoma in contrast to the surrounding tissue, as well as in human cell line and mouse models of the disease. SUMOylation of HuR promotes major cancer hallmarks, namely proliferation and invasion, whereas the absence of HuR SUMOylation results in a senescent phenotype with dysfunctional mitochondria and endoplasmic reticulum. Mechanistically, SUMOylation induces a structural rearrangement of the RNA recognition motifs that modulates HuR binding affinity to its target RNAs, further modifying the transcriptomic profile toward hepatic tumor progression. Overall, SUMOylation constitutes a mechanism of HuR regulation that could be potentially exploited as a therapeutic strategy for liver cancer.
KW - CP: Cancer
KW - CP: Molecular biology
KW - ELAVL1
KW - HCC
KW - PTMs
KW - SUMO
KW - senescence
UR - http://www.scopus.com/inward/record.url?scp=85188075086&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2024.113924
DO - 10.1016/j.celrep.2024.113924
M3 - Article
AN - SCOPUS:85188075086
SN - 2211-1247
VL - 43
JO - Cell Reports
JF - Cell Reports
IS - 3
M1 - 113924
ER -