Alternative splicing and cancer: a systematic review

Abstract

The abnormal regulation of alternative splicing is usually accompanied by the occurrence and development of tumors, which would produce multiple different isoforms and diversify protein expression. The aim of the present study was to conduct a systematic review in order to describe the regulatory mechanisms of alternative splicing, as well as its functions in tumor cells, from proliferation and apoptosis to invasion and metastasis, and from angiogenesis to metabolism. The abnormal splicing events contributed to tumor progression as oncogenic drivers and/or bystander factors. The alterations in splicing factors detected in tumors and other mis-splicing events (i.e., long non-coding and circular RNAs) in tumorigenesis were also included. The findings of recent therapeutic approaches targeting splicing catalysis and splicing regulatory proteins to modulate pathogenically spliced events (including tumor-specific neo-antigens for cancer immunotherapy) were introduced. The emerging RNA-based strategies for the treatment of cancer with abnormally alternative splicing isoforms were also discussed. However, further studies are still required to address the association between alternative splicing and cancer in more detail.

The Expanding Role of Alternative Splicing in Vascular Smooth Muscle Cell Plasticity

“…Small molecular compounds which target core factors in the spliceosome have received growing attention in the field of cancer therapeutics [ 77 , 78 ]. An abnormally high expression of splicing factors has been linked to carcinogenesis, and so, functional inhibitors have been developed to perturb tumour cell growth [ 77 , 78 ].…”

“…Small molecular compounds which target core factors in the spliceosome have received growing attention in the field of cancer therapeutics [ 77 , 78 ]. An abnormally high expression of splicing factors has been linked to carcinogenesis, and so, functional inhibitors have been developed to perturb tumour cell growth [ 77 , 78 ]. Drugs which indirectly target the SR family of splicing factors, including SRSF1, by inhibiting upstream kinases have been shown to be effective in preclinical trials [ 77 ].…”

Alternative RNA Splicing—The Trojan Horse of Cancer Cells in Chemotherapy

“…The misregulation of splicing networks and mutations affecting splicing may well result in different organ pathologies including cancer. The commencement and progression of tumorigenesis are due to gene mutations within the canonical RNA splicing sites or to alterations in the expression level of spliceosomal or splicing regulatory factors [ 17 ]. The basic processes which determine the progression and outcome of the neoplastic disease—invasion, metastasis, and angiogenesis, are also subjected to AS variations.…”

Systematic Chromosome Rearrangement Induced by CRISPR-Cas9 Reshapes the Genome and Transcriptome of Human Cells

“…p15 and p16 are cyclin-dependent kinase (CDK) inhibitors, that maintain the active state of Rb family members, and promote their binding to E2F1 21 , leading to G1 cell cycle arrest 22 . The loss of p15 and p16 helps the tumor cells bypassing the G1 cell cycle carcinogenesis 31 . Therefore, AS may be a major contribution for the SCR cells to survive the severe stress.…”