Gene-Specific Intron Retention Serves as Molecular Signature that Distinguishes Melanoma from Non-Melanoma Cancer Cells in Greek Patients

Giannopoulou, Aikaterini F.; Konstantakou, Eumorphia G.; Velentzas, Athanassios D.; Avgeris, Socratis; Avgeris, Margaritis; Παπανδρεου, Νικολαοσ; Zoi, Ilianna; Filippa, Vicky; Katarachia, Stamatia A.; Lampidonis, Antonis D.; Prombona, Anastasia; Syntichaki, Popi; Piperi, Christina; Basdra, Efthimia K.; Iconomidou, Vassiliki A.; Papadavid, Evangelia; Anastasiadou, Ema; Papassideri, Issidora S.; Papavassiliou, Athanasios G.; Voutsinas, Gerassimos E.; Scorilas, Andreas; Stravopodis, Dimitrios J.

doi:10.3390/ijms20040937

Cited by 10 publications

(7 citation statements)

References 152 publications

(189 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aberrant IR has previously been associated with disease phenotypes and clinical outcomes. For example, IR in CMYC and SESTRIN1 genes was shown to be a reliable molecular marker separating melanoma from non-melanoma tumours [ 14 ] and Sznajder and colleagues have shown that IR can be used as a biomarker in hereditary repeat expansion diseases [ 15 ]. Despite marked differences between tumour and normal breast tissue, IR profiles in our analysis also differ between ER + versus ER − tumours.…”

Section: Discussionmentioning

confidence: 99%

“…The importance of IR in cancer has been emphasized following landmark discoveries about (i) aberrant IR patterns in leukaemia [ 10 , 11 ], (ii) IR as a source of neoepitopes [ 12 ], (iii) tumour suppressor gene inactivation by intronic polyadenylation [ 13 ], (iv) IR-based biomarkers [ 14 , 15 ], and (v) IR as a therapeutic target [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Towards resolution of the intron retention paradox in breast cancer

et al. 2022

View full text Add to dashboard Cite

Background After many years of neglect in the field of alternative splicing, the importance of intron retention (IR) in cancer has come into focus following landmark discoveries of aberrant IR patterns in cancer. Many solid and liquid tumours are associated with drastic increases in IR, and such patterns have been pursued as both biomarkers and therapeutic targets. Paradoxically, breast cancer (BrCa) is the only tumour type in which IR is reduced compared to adjacent normal breast tissue. Methods In this study, we have conducted a pan-cancer analysis of IR with emphasis on BrCa and its subtypes. We explored mechanisms that could cause aberrant and pathological IR and clarified why normal breast tissue has unusually high IR. Results Strikingly, we found that aberrantly decreasing IR in BrCa can be largely attributed to normal breast tissue having the highest occurrence of IR events compared to other healthy tissues. Our analyses suggest that low numbers of IR events in breast tumours are associated with poor prognosis, particularly in the luminal B subtype. Interestingly, we found that IR frequencies negatively correlate with cell proliferation in BrCa cells, i.e. rapidly dividing tumour cells have the lowest number of IR events. Aberrant RNA-binding protein expression and changes in tissue composition are among the causes of aberrantly decreasing IR in BrCa. Conclusions Our results suggest that IR should be considered for therapeutic manipulation in BrCa patients with aberrantly low IR levels and that further work is needed to understand the cause and impact of high IR in other tumour types.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Towards resolution of the intron retention paradox in breast cancer

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Aberrant IR has previously been associated with disease phenotypes and clinical outcomes. For example, IR in CMYC and SESTRIN1 genes was shown to be a reliable molecular marker separating melanoma from non-melanoma tumours 14 and Sznajder and colleagues have shown that IR can be used as biomarker in hereditary repeat expansion diseases 15 . Despite marked differences between tumour and normal breast tissue, IR profiles in our analysis also differ between ER + vs ER − tumours.…”

Section: Discussionmentioning

confidence: 99%

“…The importance of IR in cancer has been emphasised following landmark discoveries about (i) aberrant IR patterns in leukemia 10,11 , (ii) IR as a source of neoepitopes 12 , (iii) tumour suppressor gene inactivation by intronic polyadenylation 13 , (iv) IR-based biomarkers 14,15 , and (v) IR as a therapeutic target 16 .…”

Section: Introductionmentioning

confidence: 99%

Towards resolution of the intron retention paradox in breast cancer

Shah

Milevskiy

Petrova

et al. 2022

Preprint

View full text Add to dashboard Cite

After many years of neglect in the field of alternative splicing, the importance of intron retention (IR) in cancer has come into focus following landmark discoveries of aberrant IR patterns in cancer. Many solid and liquid tumours are associated with drastic increases in IR and such patterns have been pursued as both biomarkers and therapeutic targets. Paradoxically, breast cancer (BrCa) is the only tumour type in which IR is reduced compared to adjacent normal breast tissue.In this study, we have conducted a pan-cancer analysis of IR with emphasis on BrCa and its subtypes. We explored mechanisms that could cause aberrant and pathological IR and clarified why normal breast tissue has unusually high IR.Strikingly, we found that reduced IR in BrCa can be largely attributed to normal breast tissue having the highest occurrence of IR events compared to other healthy tissues. Our analyses suggest that low numbers of IR events in breast tumours are associated with poor prognosis, particularly in the luminal B subtype. Interestingly, we found that IR frequencies negatively correlate with cell proliferation in BrCa cells, i.e. rapidly dividing tumour cells have the lowest number of IR events. Aberrant RNA binding protein (RBP) expression and changes in tissue composition are among the causes of low IR in BrCa.Our results suggest that IR should be considered for therapeutic manipulation in BrCa patients with aberrantly low IR levels and that further work is needed to understand the cause and impact of high IR in other tumour types.

show abstract

“…Complex bioinformatics was performed, and the c-MYC, SRPX2, and Sestrin-1 genes were demonstrated to undergo intron retention just in melanoma. miRNAs were generated for these genes, and thus this pattern could molecularly differentiate other skin cancers from melanoma (Giannopoulou et al, 2019).…”

Section: Discriminating Melanoma From Other Skin Cancers Through Mirnasmentioning

confidence: 99%

miRNAs in the Diagnosis and Prognosis of Skin Cancer

Neagu

Constantin

Creţoiu

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Skin cancer is, at present, the most common type of malignancy in the Caucasian population. Its incidence has increased rapidly in the last decade for both melanoma and non-melanoma skin cancer. Differential expression profiles of microRNAs (miRNAs) have been reported for a variety of different cancers, including skin cancers. Since miRNAs' discovery as regulators of gene expression, their importance grew in the field of oncology. miRNAs can post-transcriptionally regulate gene expression, tumor initiation, development progression, and aggressiveness. Nowadays, these short regulatory RNAs are perceived as one of the epigenetic markers for the identification of new diagnostic and/or prognostic molecular markers. Moreover, as miRNAs can drive tumorigenesis, they might eventually represent new therapy targets. Some miRNAs are pleiotropic, such as miR-214, which was found deregulated in several other tumors besides skin cancers. Some others are specific for one or more skin cancer types, like miR-21 and miR-221 for cutaneous melanoma and cutaneous squamous carcinoma or miR-155 for melanoma and cutaneous lymphoma. The goal of this review was to summarize some of the main miRNA detection technologies that are used to evaluate miRNAs in tissues and body fluids. Furthermore, their quantification limits, conformity, and robustness are discussed. Aberrant miRNA expression is analyzed for cutaneous melanoma, cutaneous squamous cell carcinoma (CSCC), skin lymphomas, cutaneous lymphoma, and Merkel cell carcinoma (MCC). In this type of disease, miRNAs are described as potential biomarkers to diagnose early lesion and/or early metastatic disease. In the future, whether in tissue or circulating in body fluids, miRNAs will gain their place in skin cancer diagnosis, prognosis, and future therapeutic targets.

show abstract

Gene-Specific Intron Retention Serves as Molecular Signature that Distinguishes Melanoma from Non-Melanoma Cancer Cells in Greek Patients

Cited by 10 publications

References 152 publications

Towards resolution of the intron retention paradox in breast cancer

Towards resolution of the intron retention paradox in breast cancer

Towards resolution of the intron retention paradox in breast cancer

miRNAs in the Diagnosis and Prognosis of Skin Cancer

Contact Info

Product

Resources

About