Alternative RNA splicing in stem cells and cancer stem cells: Importance of transcript-based expression analysis

Abstract

Alternative ribonucleic acid (RNA) splicing can lead to the assembly of different protein isoforms with distinctive functions. The outcome of alternative splicing (AS) can result in a complete loss of function or the acquisition of new functions. There is a gap in knowledge of abnormal RNA splice variants promoting cancer stem cells (CSCs), and their prospective contribution in cancer progression. AS directly regulates the self-renewal features of stem cells (SCs) and stem-like cancer cells. Notably, octamer-binding transcription factor 4A spliced variant of octamer-binding transcription factor 4 contributes to maintaining stemness properties in both SCs and CSCs. The epithelial to mesenchymal transition pathway regulates the AS events in CSCs to maintain stemness. The alternative spliced variants of CSCs markers, including cluster of differentiation 44, aldehyde dehydrogenase, and doublecortin-like kinase , α6β1 integrin, have pivotal roles in increasing self-renewal properties and maintaining the pluripotency of CSCs. Various splicing analysis tools are considered in this study. LeafCutter software can be considered as the best tool for differential splicing analysis and identification of the type of splicing events. Additionally, LeafCutter can be used for efficient mapping splicing quantitative trait loci. Altogether, the accumulating evidence re-enforces the fact that gene and protein expression need to be investigated in parallel with alternative splice variants.

Breastfeeding reduces the risk of breast cancer: A call for action in high‐income countries with low rates of breastfeeding

“… 53 The maintenance or differentiation of stem cells and their progenitors relies on regulation through gene expression, including chromatin modification, transcription factors, microRNAs and regulation through alternative RNA splicing. 54 , 55 The gene‐expression studies in the parous breast found genes primarily related to RNA processing and cellular differentiation. 45 , 46 Suggesting that the reduction in breast‐cancer risk associated with pregnancy may be associated with an alteration in maintenance or differentiation of breast cancer stem cells.…”

“…Studies in mice have found that an early pregnancy causes a persistent decrease in the number of functional mammary‐epithelial stem cells 53 . The maintenance or differentiation of stem cells and their progenitors relies on regulation through gene expression, including chromatin modification, transcription factors, microRNAs and regulation through alternative RNA splicing 54,55 . The gene‐expression studies in the parous breast found genes primarily related to RNA processing and cellular differentiation 45,46 .…”

Splice-disrupt genomic variants in prostate cancer

“…In humans, it is estimated that up to 94% of genes undergo alternative splicing, resulting in more than 100,000 transcripts [5][6][7]. Accumulating evidence highlights the importance of study of gene and protein in parallel with alternative splice variants [8].…”