Therefore, alternative spliced variants are potential biomarkers sellckchem [43, 44] for the cancer diagnosis/prognosis and may be the targets for cancer therapy based on specific splicing correction treatments.Single nucleotide polymorphisms (SNPs) affecting exon skipping has reviewed to confer to complex diseases [45]. The improvement of high-throughput technologies such as RNA-Seq [46, 47] and exon arrays [48, 49] is helpful to identify the genome-wide cancer-associated splicing variants. Splicing changes may associate with lung and prostate cancer risk in terms of some SNPs. For example, a coding synonymous SNP G870A of cyclin D1 (CCND1) with a modulating ability to its splice pattern was reported to be associated with lung cancer susceptibility [50].

Similarly, some coding synonymous SNPs may generate new splicing sites in the middle of an exon of p53 gene to change splicing [51]. Mutations in the adenomatous polyposis coli (APC) [52] and BRCA1 [53, 54] genes have reported to skip exon by altering splicing. Furthermore, an intronic SNP, IVS ?27G>A/IVS��A, creates a new splicing factor SR-binding site and deletes two other overlapping SR-binding sites, generating three alternative splicing forms of KLF6 (KLF6 SV1-3) [55]. This SNP was found to be associated with prostate cancer [56]. For lung cancer study, the tumor patients with overexpression of KLF6 SV1 have lower survival [56, 57].Actually, the information of many SNPs located in 3�� and 5�� splicing sites is searchable in the dbSNP in NCBI website (http://www.ncbi.nlm.nih.gov/snp) when the ��limit�� function is chosen.

Researchers may choose the SNPs of splicing sites located in interested genes to identify their association relationships to diseases and cancers. A database consisting of genome-wide SNP and splicing sites, namely, ssSNPTarget Entinostat [58] was designed to search the splice site SNPs (ssSNPs) by input of gene symbol, SNP rs number, transcript ID, or genomic position (http://variome.kobic.re.kr/ssSNPTarget/).4. Alternative Splicing-Related Drugs and Natural ProductsSplice modulating therapies have been developed for human disease [59�C61] and cancer therapy [62, 63]. Antitumor drugs have been developed to target alternative splicing [64], splice variants [65], and spliceosomes [66, 67]. For example, pharmacological interventions may be affected by mRNA transcript diversity [68]. To correct aberrant splicing, specific mRNA transcripts have been targeted in genetic disorders such as Duchenne muscular dystrophy. Since mutations of splicing factor 3B subunit 1 (SF3B1) are common in several haematological malignancies, the use of various natural products and their synthetic derivatives in therapies targeting SF3B has proven highly effective [67].