The Oncoprotein SF2/ASF Promotes Non-Small Cell Lung Cancer Survival by Enhancing Survivin Expression

摘要

Regulation of mRNA metabolism (processing, export, localization, surveillance, translation, and decay) contributes more relevantly than previously suspected to the genesis of a great variety of diseases, including cancer (1-7). Modifications in the levels of mRNA processing proteins can elicit global changes in the profile of mRNA expression, affecting a number of cancer-associated genes. In lung cancer, the leading cause of cancer mortality (8), several studies have shown changes in the expression of members of two families of mRNA processing proteins: heterogeneous nuclear ribonucleoproteins (hnRNP) and serine/arginine (SR)-rich proteins (9-11). Elevated expression of hnRNP A1 and the SR protein SF2/ASF has been related to the presence of metastasis-associated alternative splicing isoforms of CD44 in a mouse model of lung cancer (10). SF2/ASF has been recently found to be upre-gulated in several human neoplasias, and has been described as an oncoprotein with roles in the establishment and maintenance of transformation (12). SF2/ASF plays a role in several key features of RNA metabolism, such as mRNA constitutive and alternative splicing, nuclear export, stability, and translation (13-17).