SENEBLOC, a long non-coding RNA suppresses senescence via p53-dependent and independent mechanisms.

Xu, Cheng Lin; Sang, Ben; Liu, Guang Zhi; Li, Jin Ming; Zhang, Xu Dong; Liu, Lian Xin; Thorne, Rick F; Wu, Mian

Xu, Cheng Lin; Sang, Ben; Liu, Guang Zhi; Li, Jin Ming; Zhang, Xu Dong; Liu, Lian Xin; Thorne, Rick F; Wu, Mian.

Afiliación

Xu CL; CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Centre for Excellence in Molecular Cell Science, School of Life Sciences and First Affiliated Hospital of University of Science and Technology of China, Hefei 230027, China.
Sang B; CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Centre for Excellence in Molecular Cell Science, School of Life Sciences and First Affiliated Hospital of University of Science and Technology of China, Hefei 230027, China.
Liu GZ; Key Laboratory of Stem Cell Differentiation & Modification, School of Clinical Medicine, Henan University, Zhengzhou 450003, China.
Li JM; Translational Research Institute, Henan Provincial People's Hospital, Academy of Medical Science, Zhengzhou University, Zhengzhou 450053, China.
Zhang XD; Translational Research Institute, Henan Provincial People's Hospital, Academy of Medical Science, Zhengzhou University, Zhengzhou 450053, China.
Liu LX; School of Biomedical Sciences & Pharmacy, University of Newcastle, NSW 2308, Australia.
Thorne RF; CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Centre for Excellence in Molecular Cell Science, School of Life Sciences and First Affiliated Hospital of University of Science and Technology of China, Hefei 230027, China.
Wu M; Translational Research Institute, Henan Provincial People's Hospital, Academy of Medical Science, Zhengzhou University, Zhengzhou 450053, China.

Nucleic Acids Res ; 48(6): 3089-3102, 2020 04 06.

Article en En | MEDLINE | ID: mdl-32030426

RESUMEN

Long non-coding RNAs (lncRNAs) have emerged as important biological tuners. Here, we reveal the role of an uncharacterized lncRNA we call SENEBLOC that is expressed by both normal and transformed cells under homeostatic conditions. SENEBLOC was shown to block the induction of cellular senescence through dual mechanisms that converge to repress the expression of p21. SENEBLOC facilitates the association of p53 with MDM2 by acting as a scaffold to promote p53 turnover and decrease p21 transactivation. Alternatively, SENEBLOC was shown to affect epigenetic silencing of the p21 gene promoter through regulation of HDAC5. Thus SENEBLOC drives both p53-dependent and p53-independent mechanisms that contribute to p21 repression. Moreover, SENEBLOC was shown to be involved in both oncogenic and replicative senescence, and from the perspective of senolytic agents we show that the antagonistic actions of rapamycin on senescence are dependent on SENEBLOC expression.

Asunto(s)

Envejecimiento/genética; Neoplasias/genética; ARN Largo no Codificante/genética; Proteína p53 Supresora de Tumor/genética; Animales; Carcinogénesis/genética; Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética; Regulación Neoplásica de la Expresión Génica/genética; Células HCT116; Xenoinjertos; Histona Desacetilasas/genética; Humanos; Ratones; Unión Proteica/genética; Transducción de Señal/genética

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: Envejecimiento / Proteína p53 Supresora de Tumor / ARN Largo no Codificante / Neoplasias Límite: Animals / Humans Idioma: En Revista: Nucleic Acids Res Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google