The H19 Long non-coding RNA in cancer initiation, progression and metastasis – a proposed unifying theory

Molecular Cancer

Review

Imad J. Matouk¹  Michal Gilon¹  Abraham Hochberg¹  Eli Raveh¹ 

[1] The Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Faculty of Sciences, The Edmond J. Safra Campus, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel;

关键词: H19;    miR-675;    Tumorigenesis;    Proliferation;    Differentiation;    EMT;    MET;    Genomic instability;    miR-200;    let-7;   

DOI  :  10.1186/s12943-015-0458-2

 received in 2015-06-23, accepted in 2015-10-20,  发布年份 2015

来源: Springer

【 摘 要 】

The imprinted oncofetal long non-coding RNA (lncRNA) H19 is expressed in the embryo, down-regulated at birth and then reappears in tumors. Its role in tumor initiation and progression has long been a subject of controversy, although accumulating data suggest that H19 is one of the major genes in cancer. It is actively involved in all stages of tumorigenesis and is expressed in almost every human cancer. In this review we delineate the various functions of H19 during the different stages in the complex process of tumor progression. H19 up-regulation allows cells to enter a “selfish” survival mode in response to stress conditions, such as destabilization of the genome and hypoxia, by accelerating their proliferation rate and increasing overall cellular resistance to stress. This response is tightly correlated with nullification, dysfunction or significant down-regulation of the master tumor suppressor gene P53. The growing evidence of H19’s involvement in both proliferation and differentiation processes, together with its involvement in epithelial to mesenchymal transition (EMT) and also mesenchymal to epithelial transition (MET), has led us to conclude that some of the recent disputes and discrepancies arising from current research findings can be resolved from a viewpoint supporting the oncogenic properties of H19. According to a holistic approach, the versatile, seemingly contradictory functions of H19 are essential to, and differentially harnessed by, the tumor cell depending on its context within the process of tumor progression.

【 授权许可】

CC BY   
© Raveh et al. 2015