PMC:3480681 / 9798-12865 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3480681","sourcedb":"PMC","sourceid":"3480681","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3480681","text":"Alternative Splicing in Cancer\nA number of studies have been reported that alternative splicing is related closely to development, cellular stress, and various diseases, including cancer, as a crucial contributor to transcriptome and proteome diversity [1, 7, 8, 14]. In cancer, with increasing genomic instability, sequence substitution and aberrant alternative splicing occur frequently, leading to erroneous and dysfunctional proteins [14]. Protein isoforms made from this process are developmentally regulated and preferentially re-expressed in cancer and help the differentiation and survival of cancer cells (Fig. 2). The development of genomewide analysis allows large-scale examination of the relationship between alternative splicing and tumorigenesis [40, 41]. Every case of alternative splicing is reported in cancer; among these, the most frequent case is the mutually exclusive exon [14]. For example, overexpression of CD44, involved in cell proliferation, differentiation, migration, and alternative splicing, by different splice sites of CD44 during tumorigenesis indicates that it could play roles in tumor cell invasion and metastasis [42-45]. Tumor suppressor genes, such as p53 and PTEN (Phosphatase and Tensin homolog, deleted on chromosome TEN), have splicing variants associated to cancer [46]. p53 protein isoforms through alternative splicing have critical roles in many biological processes, indicating that dysregulation effects tumorigenesis [47]. Different expression of PTEN and its alternatively spliced transcripts are found to vary in different tissue types. PTEN regulates p53 stability and in turn regulates its own transcriptional activity. The PTEN splice variants retained in intron 3 region and intron 5 region have been found in breast cancer [46]. In the case of the APC gene, aberrant splice skipping of exon 4, created by insertion of T in intron 4, is involved in colon cancer [48]. An alternative 5' splice site in BCL-X results in 2 isoforms, long and short (Bcl-x (L), Bcl-x (X)), which have contrasting functions related to apoptosis and are overexpressed in various tumors [49, 50]. Although specific roles of vascular endothelial growth factor (VEGF) isoforms are not known exactly, among the isoforms of VEGF4 involved in formation of new vessels, VEGF165 and VEGF165b, created by an alternative 3' splice site, have different expression in cancer [51, 52]. Over 40 different MDM2 transcripts are identified in normal and cancer by alternative 5' and 3' splice sites. They mostly lose the p53 binding domain and promote tumor progression and affect prognosis independently [53, 54]. Increasing number of reports have demonstrated the expression of aberrant and abnormal splice variants in cancer cells or tissues. However, it is not enough evidence for a functional relationship between alternative splicing and cancer. Hallmarks of the initiation and early growth of cancers during tumor progression using large-scale analyses of splicing variants in the cancer EST database are needed as new RNA prognosis markers.","divisions":[{"label":"Title","span":{"begin":0,"end":30}}],"tracks":[{"project":"2_test","denotations":[{"id":"23105933-17395108-44845893","span":{"begin":254,"end":255},"obj":"17395108"},{"id":"23105933-15234240-44845894","span":{"begin":257,"end":258},"obj":"15234240"},{"id":"23105933-17416541-44845895","span":{"begin":260,"end":261},"obj":"17416541"},{"id":"23105933-15520162-44845896","span":{"begin":263,"end":265},"obj":"15520162"},{"id":"23105933-15520162-44845897","span":{"begin":439,"end":441},"obj":"15520162"},{"id":"23105933-21041405-44845898","span":{"begin":762,"end":764},"obj":"21041405"},{"id":"23105933-19448617-44845899","span":{"begin":766,"end":768},"obj":"19448617"},{"id":"23105933-15520162-44845900","span":{"begin":897,"end":899},"obj":"15520162"},{"id":"23105933-10380879-44845901","span":{"begin":1154,"end":1156},"obj":"10380879"},{"id":"23105933-12484499-44845901","span":{"begin":1154,"end":1156},"obj":"12484499"},{"id":"23105933-12600935-44845901","span":{"begin":1154,"end":1156},"obj":"12600935"},{"id":"23105933-15648050-44845901","span":{"begin":1154,"end":1156},"obj":"15648050"},{"id":"23105933-21893034-44845902","span":{"begin":1313,"end":1315},"obj":"21893034"},{"id":"23105933-22007292-44845903","span":{"begin":1471,"end":1473},"obj":"22007292"},{"id":"23105933-21893034-44845904","span":{"begin":1784,"end":1786},"obj":"21893034"},{"id":"23105933-15131404-44845905","span":{"begin":1922,"end":1924},"obj":"15131404"},{"id":"23105933-9263629-44845906","span":{"begin":2123,"end":2125},"obj":"9263629"},{"id":"23105933-11431734-44845907","span":{"begin":2127,"end":2129},"obj":"11431734"},{"id":"23105933-15520188-44845908","span":{"begin":2400,"end":2402},"obj":"15520188"},{"id":"23105933-17595666-44845909","span":{"begin":2404,"end":2406},"obj":"17595666"},{"id":"23105933-12150820-44845910","span":{"begin":2625,"end":2627},"obj":"12150820"},{"id":"23105933-14757843-44845911","span":{"begin":2629,"end":2631},"obj":"14757843"}],"attributes":[{"subj":"23105933-17395108-44845893","pred":"source","obj":"2_test"},{"subj":"23105933-15234240-44845894","pred":"source","obj":"2_test"},{"subj":"23105933-17416541-44845895","pred":"source","obj":"2_test"},{"subj":"23105933-15520162-44845896","pred":"source","obj":"2_test"},{"subj":"23105933-15520162-44845897","pred":"source","obj":"2_test"},{"subj":"23105933-21041405-44845898","pred":"source","obj":"2_test"},{"subj":"23105933-19448617-44845899","pred":"source","obj":"2_test"},{"subj":"23105933-15520162-44845900","pred":"source","obj":"2_test"},{"subj":"23105933-10380879-44845901","pred":"source","obj":"2_test"},{"subj":"23105933-12484499-44845901","pred":"source","obj":"2_test"},{"subj":"23105933-12600935-44845901","pred":"source","obj":"2_test"},{"subj":"23105933-15648050-44845901","pred":"source","obj":"2_test"},{"subj":"23105933-21893034-44845902","pred":"source","obj":"2_test"},{"subj":"23105933-22007292-44845903","pred":"source","obj":"2_test"},{"subj":"23105933-21893034-44845904","pred":"source","obj":"2_test"},{"subj":"23105933-15131404-44845905","pred":"source","obj":"2_test"},{"subj":"23105933-9263629-44845906","pred":"source","obj":"2_test"},{"subj":"23105933-11431734-44845907","pred":"source","obj":"2_test"},{"subj":"23105933-15520188-44845908","pred":"source","obj":"2_test"},{"subj":"23105933-17595666-44845909","pred":"source","obj":"2_test"},{"subj":"23105933-12150820-44845910","pred":"source","obj":"2_test"},{"subj":"23105933-14757843-44845911","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93ece3","default":true}]}]}}