Alternative Splicing for Diseases, Cancers, Drugs, and Databases

Tang, Jen‐Yang; Lee, Jin‐Ching; Hou, Ming‐Feng; Wang, Chunlin; Chen, Chien-Chi; Huang, Hurng‐Wern; Chang, Hsueh-Wei

doi:10.1155/2013/703568

Cited by 37 publications

(23 citation statements)

References 132 publications

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“…This is in accordance to the results obtained by Roca and colleagues [47] when they analysed the determinants of the inherent strength of human 5′ splice sites. They showed that when there is extensive complementarity to U1 snRNA, the donor sequence exerts a dominant effect for 5′ss selection, but in the case of competing 5′ss with similarly modest complementarily to U1, the role of other 5′ss features is more prominent [48].…”

Section: Discussionmentioning

confidence: 99%

Comparative ex vivo, in vitro and in silico analyses of a CFTR splicing mutation: Importance of functional studies to establish disease liability of mutations

Ramalho

Clarke

Sousa

et al. 2016

Journal of Cystic Fibrosis

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The Cystic Fibrosis p.Ile1234Val missense mutation actually creates a new dual splicing site possibly used either as a new acceptor or donor. Here, we aimed to test the accuracy of in silico predictions by comparing them with in vitro and ex vivo functional analyses of this mutation for an accurate CF diagnosis/prognosis. To this end, we applied a new in vitro strategy using a CFTR mini-gene which includes the complete CFTR coding sequence plus intron 22 (short version) which allows the assessment of alternatively spliced mRNA levels as well as the properties of the resulting abnormal CFTR protein regarding processing, intracellular localization and function. Our data demonstrate that p.Ile1234Val leads to usage of the alternative splicing donor (but not acceptor) resulting in alternative CFTR transcripts lacking 18 nts of exon 22 which produce a truncated CFTR protein with residual Cl- channel function. These results recapitulate data from native tissues of a CF patient. In conclusion, the existing in silico prediction models have limited application and ex vivo functional assessment of mutation effects should be made. Alternatively the in vitro strategy adopted here can be applied to assess the disease liability of mutations for an accurate CF diagnosis/prognosis.

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Section: Discussionmentioning

confidence: 99%

Comparative ex vivo, in vitro and in silico analyses of a CFTR splicing mutation: Importance of functional studies to establish disease liability of mutations

Ramalho

Clarke

Sousa

et al. 2016

Journal of Cystic Fibrosis

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“…Alternative splicing usually mediates changes in protein structure, function, and localization, which are implicated in diseases, cancers, and drug resistance (Reviewed in (Tang et al 2013). Research on RNA splicing contributes to the understanding of cancer diagnosis, prognosis and treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Abnormality in the splicing process may affect the progression of various human diseases (Kornblihtt et al, 2013;Tang et al, 2013). Eukaryotic pre-mRNAs are transcribed from genomic DNA and spliced to form mature mRNAs.…”

mentioning

confidence: 99%

“…Eukaryotic pre-mRNAs are transcribed from genomic DNA and spliced to form mature mRNAs. The pre-mRNA alternative splicing, a process in which intronic regions and exonic sequences are destined to be removed, greatly increases the diversity and complexity of gene expression (Tang et al, 2013). Alternative splicing that affects the protein coding gene of mRNA gives rise to proteins that differ in their sequence and therefore in their activities.…”

mentioning

confidence: 99%

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Alternative Messenger RNA Splicing of Autophagic Gene Beclin 1 in Human B-cell Acute Lymphoblastic Leukemia Cells

Niu¹,

Liu²,

Zhang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Beclin 1 is a key factor for initiation and regulation of autophagy, which is a cellular catabolic process involved in tumorigenesis. To investigate the role of alternative splicing of Beclin1 in the regulation of autophagy in leukemia cells, Beclin1 mRNA from 6 different types of cell lines and peripheral blood mononuclear cells from 2 healthy volunteers was reversely transcribed, subcloned, and screened for alternative splicing. New transcript variants were analyzed by DNA sequencing. A transcript variant of Beclin 1 gene carrying a deletion of exon 11, which encoded a C-terminal truncation of Beclin 1 isoform, was found. The alternative isoform was assessed by bioinformatics, immunoblotting and subcellular localization. The results showed that this variable transcript is generated by alternative 3' splicing, and its translational product displayed a reduced activity in induction of autophagy by starvation, indicating that the spliced isoform might function as a dominant negative in leukemogenesis regulated by autophagy.

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“…The vast majority of protein-coding genes have alternative splicing isoforms, which display diverse or even opposite function and might lead to cell dysfunction (Tang et al, 2013). It is now evident that the unbalanced expression of splicing variants or the failure to properly express the correct isoforms is part of the biology of cancer cells (Pajares et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Alternative splicing isoform of T cell factor 4K suppresses the proliferation and metastasis of non-small cell lung cancer cells

Fan¹,

Lü²,

Chen³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The Wnt pathway has been implicated in the initiation, progression, and metastasis of lung cancer. T cell factor 4, a member of TCF/LEF family, acts as a transcriptional factor for Wnt pathways in lung cancer. Increasing amounts of evidence have shown that TCF-4 has multiple alternative splicing isoforms with transactivation or transrepression activity toward the Wnt pathway. Here, we found the presence of multiple TCF-4 isoforms in lung cancer cell lines and in normal bronchial epithelial cells. TCF-4K isoform expression was significantly decreased in lung cancer cells compared with normal bronchial epithelial cells and was identified as a transcriptional suppressor of the Wnt pathway in non-small cell lung carcinoma (NSCLC). Overexpression of TCF-4K significantly inhibited the proliferation and migration of NSCLC cells. Collectively, our data indicate that TCF-4K functions as a tumor suppressor in NSCLC by down-regulating the Wnt pathway.

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Alternative Splicing for Diseases, Cancers, Drugs, and Databases

Cited by 37 publications

References 132 publications

Comparative ex vivo, in vitro and in silico analyses of a CFTR splicing mutation: Importance of functional studies to establish disease liability of mutations

Comparative ex vivo, in vitro and in silico analyses of a CFTR splicing mutation: Importance of functional studies to establish disease liability of mutations

Alternative Messenger RNA Splicing of Autophagic Gene Beclin 1 in Human B-cell Acute Lymphoblastic Leukemia Cells

Alternative splicing isoform of T cell factor 4K suppresses the proliferation and metastasis of non-small cell lung cancer cells

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