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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
Alternative splicing and tumor progression
Claudia Ghigna1, Cristina Valacca, Giuseppe Biamonti
1Istituto di Genetica Molecolare - Consiglio Nazionale delle Ricerche, Via Abbiategrasso 207. 27100 Pavia, Italy.
Abstract:
Alternative splicing is a key molecular mechanism for increasing the functional diversity of the eukaryotic proteomes. A large body of experimental data implicates aberrant splicing in various human diseases, including cancer. Both mutations in cis-acting splicing elements and alterations in the expression and/or activity of splicing regulatory factors drastically affect the splicing profile of many cancer-associated genes. In addition, the splicing profile of several cancer-associated genes is altered in particular types of cancer arguing for a direct role of specific splicing isoforms in tumor progression. Deciphering the mechanisms underlying aberrant splicing in cancer may prove crucial to understand how splicing machinery is controlled and integrated with other cellular processes, in particular transcription and signaling pathways. Moreover, the characterization of splicing deregulation in cancer will lead to a better comprehension of malignant transformation. Cancer-associated alternative splicing variants may be new tools for the diagnosis and classification of cancers and could be the targets for innovative therapeutical interventions based on highly selective splicing correction approaches.
Insights
Alternative splicing dysregulation is common in cancer, impacting gene function and tumor progression. Understanding these splicing changes offers new diagnostic and therapeutic strategies for cancer.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Alternative splicing significantly expands proteome diversity in eukaryotes.
- Aberrant alternative splicing is implicated in numerous human diseases, notably cancer.
- Splicing alterations in cancer arise from genetic mutations and changes in regulatory factors.
Purpose of the Study:
- To investigate the role of aberrant splicing in cancer development and progression.
- To understand the interplay between splicing, transcription, and signaling pathways in cancer.
- To explore cancer-associated splicing variants as diagnostic markers and therapeutic targets.
Main Methods:
- Analysis of cis-acting splicing elements and splicing regulatory factors in cancer-associated genes.
- Examination of splicing profiles in various cancer types.
- Investigating the functional impact of specific splicing isoforms on tumor progression.
Main Results:
- Mutations and altered regulatory factor activity significantly impact cancer gene splicing.
- Specific splicing profiles are associated with distinct cancer types, suggesting isoform-specific roles.
- Aberrant splicing is linked to malignant transformation and tumor progression.
Conclusions:
- Deciphering aberrant splicing mechanisms is crucial for understanding cancer biology.
- Cancer-associated splicing variants hold potential for novel cancer diagnostics and therapeutics.
- Targeting splicing correction offers a promising avenue for innovative cancer treatments.
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