2020
DOI: 10.3390/cells9030760
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Transcription Factors in Cancer: When Alternative Splicing Determines Opposite Cell Fates

Abstract: Alternative splicing (AS) is a finely regulated mechanism for transcriptome and proteome diversification in eukaryotic cells. Correct balance between AS isoforms takes part in molecular mechanisms that properly define spatiotemporal and tissue specific transcriptional programs in physiological conditions. However, several diseases are associated to or even caused by AS alterations. In particular, multiple AS changes occur in cancer cells and sustain the oncogenic transcriptional program. Transcription factors … Show more

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Cited by 54 publications
(40 citation statements)
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References 178 publications
(211 reference statements)
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“…Some transcription factors splice variants can exert dominant negative (DN) activity hampering the physiological function of long isoforms, associating their expression with different cancer phenotypes. The DN activity of short isoforms can relate to cellular mislocalization and/or sequestration of the functional transcription factor ( Belluti et al, 2020 ). For instance, the Ikaros Family Zinc Finger Protein HELIOS expresses three DN isoforms with cytoplasmic localization in human leukemic T-cell lines, unbalancing the expression of functional variants.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Some transcription factors splice variants can exert dominant negative (DN) activity hampering the physiological function of long isoforms, associating their expression with different cancer phenotypes. The DN activity of short isoforms can relate to cellular mislocalization and/or sequestration of the functional transcription factor ( Belluti et al, 2020 ). For instance, the Ikaros Family Zinc Finger Protein HELIOS expresses three DN isoforms with cytoplasmic localization in human leukemic T-cell lines, unbalancing the expression of functional variants.…”
Section: Discussionmentioning
confidence: 99%
“…From the same family, IKAROS, a transcription factor that plays a central role in hematopoiesis, presents shorter isoforms that cannot bind DNA and impair the DNA-binding activity of longer IKAROS variants. In this sense, short DN isoforms reduce IKAROS activity in hematopoiesis regulation, correlating with blast crisis development in patients with different types of leukemia ( Belluti et al, 2020 ). Whether the short_E1A isoform falls in any of these categories will require further investigation.…”
Section: Discussionmentioning
confidence: 99%
“…Previous studies have already detected the survival-associated alternative splicing events or differentially splicing events involved in specific exons as the prognostic biomarker or drug response biomarker in different human cancers [ 50 , 51 , 52 , 53 ]. It has also been reported that the different alternative splicing events occurring in the same gene show opposite prognostic effects in the same cancer type [ 50 , 51 ], suggesting that these protein isoforms may have diverse or even opposite biological functions [ 54 ]. In this study, we only focus on the expression of different alternatively spliced transcripts of PKM and explore the potential biology functions and prognostic effects in different cancers.…”
Section: Discussionmentioning
confidence: 99%
“…CEBPB not only facilitates viral transcription [68,69] but also contributes to HCC cell proliferation and invasion [70] and predating pathogenic events subsuming inflammation, endoplasmic reticulum stress and hepatic steatosis when highly expressed [71]. Hence, the control of CEBPB would inhibit both the virus and carcinogenesis [72]. Likewise, HSPs not only expedite viral replication [40,41] but also participate in cancers including HCC [73,74].…”
Section: Discussionmentioning
confidence: 99%