Abstract
BackgroundAlternative splicing commonly occurs in cancer cells and many cancer specific splice variants have been reported as potential candidate biomarkers of the disease. We have studied human tissue Kallikrein 7 (KLK7) mRNA expression profile in breast cancer patients of our region. KLK7 is member of a multi-gene family consisting of 15 members (KLK1-KLK15).MethodsWe optimized touch down nested PCR method for the amplification of KLK7 isoforms/variants. Various bioinformatics tools were used for sequence analysis, identification of splicing pattern and prediction of encoded proteins.ResultsWe observed an unusual splicing event consisting of exon 3 (E3) truncation at 3′ end (by 124 nucleotides), exon 4 (E4) exclusion and exon 5 (E5) truncation at 5′ end (by 33 nucleotide) in 2 normal breast tissues, one obtained from invasive ductal carcinoma grade II patient and other collected from mammary dysplasia patient. Moreover, 3 other KLK7 mRNAs (KF963190, KF963191, and KF963193) expressed in breast cancer were noticed to exhibit single nucleotide polymorphism (SNPs). Bioinformatic analysis revealed that the alternatively spliced mRNA (KF963192) will potentially encode a truncated and non-functional protein. Similarly although encoded proteins have considerable homology with normal hK7 protein, SNPs seem to cause great variations in pIs, structures and molecular weights of encoded proteins.ConclusionsThere is need to further explore the impact of the unique splicing event, SNPs and characterize these population specific mutations and their possible role in the pathogenesis of breast cancer.Graphical abstract
Highlights
Alternative splicing commonly occurs in cancer cells and many cancer specific splice variants have been reported as potential candidate biomarkers of the disease
Spliced variant is a novel variant because it is generated by the combined effect of three splicing events including exclusion of exon 4 (E4) and truncations of the flanking exons exon 3 (E3) and exon 5 (E5) at 3′ and 5′ ends, respectively
Simultaneous exclusion of multiple adjacent exons has already been reported in mouse intercellular cell adhesion molecule 1 (ICAM-1) gene [29] but the splicing event that has been observed in case of Human tissue Kallikrein 7 gene (KLK7) mRNA4 is unique because such splicing scheme has not been reported earlier
Summary
Alternative splicing commonly occurs in cancer cells and many cancer specific splice variants have been reported as potential candidate biomarkers of the disease. Alternative splicing is a way to produce functionally diverse proteins from a single gene [1, 2]. It occurs in a variety of biological processes including developmental, physiological and pathogenic pathways [3]. Few KLK splice variants help in cancer diagnosis and prognosis [7,8,9] and can be used as potential biomarkers of cancer [10, 11]. Future work in this area will be helpful to find more useful diagnostic and prognostic biomarkers [12]
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