The functional role of alternative splicing variants in cancer progression

Abstract

Alternative pre-mRNA processing is an important regulator of gene expres-sion because it produces sufficient copies of the use of genetic information, in which exons remain and introns are removed. Thus, alternative splicing is an important mechanism for gene regulation and genetic diversity. Jumonji Domain Containing6 (JMJD6) is a histone arginine dimethylase that allows the dynamic regulation of transcription by preferentially removing the methyl group form the arginine 3 of histone 4 (H4R3me2) and the demethylated arginine 2 of histone 3 (H3R2me2). JMJD6 also regulates gene expression by regulating RNA splicing, suggesting that JMJD6 is a multifaceted epigenetic regulator. Clinically, overexpression of JMJD6 is closely associated with poor prognosis in a variety of human cancers, including lung and breast. JMJD6 has been reported to promote cancer cell migration, invasion and angiogenic sprouting, two phenotypes of which are well known for cancer stem cell (CSC; known as cancer-causing cells) characteristics. Recent studies have reported that alternative splicing are closely associated with various diseases, including cancer. However, its functional consequence of cancer progression remains unknown. We have been discovered the cancer-related JMJD6 transcript variants through cancer database analysis. In this study, we identify two distinct protein of JMJD6 that differential ex-pression changes in cancer tissues: full-length JMJD6 mRNA expression de-creased in cancer, whereas truncated JMJD6 mRNA expression increased in cancer, compared to normal tissue. We suggest that truncated JMJD6 mRNA by alternative splicing is mainly associated with cancer.