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Regulation of RNA Splicing: Aberrant Splicing Regulation and Therapeutic Targets in Cancer

期刊

CELLS
卷 10, 期 4, 页码 -

出版社

MDPI
DOI: 10.3390/cells10040923

关键词

RNA splicing; aberrant splicing; cancer; splicing factor; splicing variant; non-coding RNA; treatment targeting splicing

资金

  1. JSPS KAKENHI [JP19K18804]
  2. Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from the AMED [JP19am0101084]
  3. Daicel Inc. (Osaka, Japan)
  4. Cell Science Research Foundation
  5. Foundation of Kinoshita Memorial Enterprise

向作者/读者索取更多资源

RNA splicing is a crucial process in the maturation of mRNA, allowing for diversity in mature mRNA through the inclusion and exclusion of introns and exons. Cancer cells develop cancer-specific mechanisms through abnormal splicing regulation to resist treatment and promote malignancy. Dysregulation of splicing is caused by factors such as mutations in splicing factors and changes in genomic sequences, impacting the splicing profile related to cancer.
RNA splicing is a critical step in the maturation of precursor mRNA (pre-mRNA) by removing introns and exons. The combination of inclusion and exclusion of introns and exons in pre-mRNA can generate vast diversity in mature mRNA from a limited number of genes. Cancer cells acquire cancer-specific mechanisms through aberrant splicing regulation to acquire resistance to treatment and to promote malignancy. Splicing regulation involves many factors, such as proteins, non-coding RNAs, and DNA sequences at many steps. Thus, the dysregulation of splicing is caused by many factors, including mutations in RNA splicing factors, aberrant expression levels of RNA splicing factors, small nuclear ribonucleoproteins biogenesis, mutations in snRNA, or genomic sequences that are involved in the regulation of splicing, such as 5' and 3' splice sites, branch point site, splicing enhancer/silencer, and changes in the chromatin status that affect the splicing profile. This review focuses on the dysregulation of RNA splicing related to cancer and the associated therapeutic methods.

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