Editorial
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World J Gastroenterol. Jul 7, 2010; 16(25): 3091-3102
Published online Jul 7, 2010. doi: 10.3748/wjg.v16.i25.3091
Impairment of pre-mRNA splicing in liver disease: Mechanisms and consequences
Carmen Berasain, Saioa Goñi, Josefa Castillo, María Ujue Latasa, Jesús Prieto, Matías A Ávila
Carmen Berasain, Saioa Goñi, Josefa Castillo, María Ujue Latasa, Jesús Prieto, Matías A Ávila, Division of Hepatology and Gene Therapy, CIMA, University of Navarra, Pamplona 31008, Spain
Author contributions: All authors contributed equally to this paper; Berasain C and Ávila MA wrote the paper.
Supported by The Agreement between FIMA and the “UTE project CIMA”; Red Temática de Investigación Cooperativa en Cáncer RD06 00200061 (to Berasain C and Ávila MA), and Ciberehd (to Prieto J) from Instituto de Salud Carlos III; Grants FIS PI070392 and PI070402 from Ministerio de Sanidad y Consumo; Goñi S was supported by a fellowship from Ministerio de Sanidad y Consumo; Latasa MU and Castillo J were supported by a Ramón y Cajal contract and a Torres Quevedo contract from Ministerio de Educación y Ciencia, respectively
Correspondence to: Matías A Ávila, PhD, Professor of Biochemistry, Division of Hepatology and Gene Therapy, CIMA, University of Navarra, Pamplona 31008, Spain. maavila@unav.es
Telephone: +34-948-194700 Fax: +34-948-194717
Received: February 22, 2010
Revised: April 12, 2010
Accepted: April 19, 2010
Published online: July 7, 2010
Abstract

Pre-mRNA splicing is an essential step in the process of gene expression in eukaryotes and consists of the removal of introns and the linking of exons to generate mature mRNAs. This is a highly regulated mechanism that allows the alternative usage of exons, the retention of intronic sequences and the generation of exonic sequences of variable length. Most human genes undergo splicing events, and disruptions of this process have been associated with a variety of diseases, including cancer. Hepatocellular carcinoma (HCC) is a molecularly heterogeneous type of tumor that usually develops in a cirrhotic liver. Alterations in pre-mRNA splicing of some genes have been observed in liver cancer, and although still scarce, the available data suggest that splicing defects may have a role in hepatocarcinogenesis. Here we briefly review the general mechanisms that regulate pre-mRNA splicing, and discuss some examples that illustrate how this process is impaired in liver tumorigenesis, and may contribute to HCC development. We believe that a more thorough examination of pre-mRNA splicing is still needed to accurately draw the molecular portrait of liver cancer. This will surely contribute to a better understanding of the disease and to the development of new effective therapies.

Keywords: Cell signalling; Hepatocarcinogenesis; Pre-mRNA splicing; Splicing factors; Targeted anticancer therapy