Impact of Alternative Splicing Variants on Liver Cancer Biology

Cancers

Matias A. Avila¹  Carmen Berasain¹  Maitane Asensio²  Maria Reviejo²  Elisa Lozano²  Jose J. G. Marin²  Meraris Soto²  Sara Ortiz-Rivero²  Elisa Herraez² 

[1] Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, 28029 Madrid, Spain;Experimental Hepatology and Drug Targeting (HEVEPHARM), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain;

关键词: alternative splicing;    carcinogenesis;    chemotherapy;    cholangiocarcinoma;    hepatocellular carcinoma;    metastasis;   

DOI  :  10.3390/cancers14010018

来源: DOAJ

【 摘 要 】

The two most frequent primary cancers affecting the liver, whose incidence is growing worldwide, are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), which are among the five most lethal solid tumors with meager 5-year survival rates. The common difficulty in most cases to reach an early diagnosis, the aggressive invasiveness of both tumors, and the lack of favorable response to pharmacotherapy, either classical chemotherapy or modern targeted therapy, account for the poor outcome of these patients. Alternative splicing (AS) during pre-mRNA maturation results in changes that might affect proteins involved in different aspects of cancer biology, such as cell cycle dysregulation, cytoskeleton disorganization, migration, and adhesion, which favors carcinogenesis, tumor promotion, and progression, allowing cancer cells to escape from pharmacological treatments. Reasons accounting for cancer-associated aberrant splicing include mutations that create or disrupt splicing sites or splicing enhancers or silencers, abnormal expression of splicing factors, and impaired signaling pathways affecting the activity of the splicing machinery. Here we have reviewed the available information regarding the impact of AS on liver carcinogenesis and the development of malignant characteristics of HCC and iCCA, whose understanding is required to develop novel therapeutical approaches aimed at manipulating the phenotype of cancer cells.

【 授权许可】

Unknown