Aberrant Dyskerin Expression Is Related to Proliferation and Poor Survival in Endometrial Cancer
Dyskerin is a core-component of the telomerase holo-enzyme, which elongates telomeres. Telomerase is involved in endometrial epithelial cell proliferation. Most endometrial cancers (ECs) have high telomerase activity; however, dyskerin expression in human healthy endometrium or in endometrial pathol...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/2/273 |
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| author | Rafah Alnafakh Gabriele Saretzki Angela Midgley James Flynn Areege M. Kamal Lucy Dobson Purushothaman Natarajan Helen Stringfellow Pierre Martin-Hirsch Shandya B. DeCruze Sarah E. Coupland Dharani K. Hapangama |
| author_facet | Rafah Alnafakh Gabriele Saretzki Angela Midgley James Flynn Areege M. Kamal Lucy Dobson Purushothaman Natarajan Helen Stringfellow Pierre Martin-Hirsch Shandya B. DeCruze Sarah E. Coupland Dharani K. Hapangama |
| author_sort | Rafah Alnafakh |
| collection | DOAJ |
| description | Dyskerin is a core-component of the telomerase holo-enzyme, which elongates telomeres. Telomerase is involved in endometrial epithelial cell proliferation. Most endometrial cancers (ECs) have high telomerase activity; however, dyskerin expression in human healthy endometrium or in endometrial pathologies has not been investigated yet. We aimed to examine the expression, prognostic relevance, and functional role of dyskerin in human EC. Endometrial samples from a cohort of 175 women were examined with immunohistochemistry, immunoblotting, and qPCR. The EC cells were transfected with Myc-DDK-DKC1 plasmid and the effect of dyskerin overexpression on EC cell proliferation was assessed by flow cytometry. Human endometrium expresses dyskerin (<i>DKC1</i>) and dyskerin protein levels are significantly reduced in ECs when compared with healthy postmenopausal endometrium. Low dyskerin immunoscores were potentially associated with worse outcomes, suggesting a possible prognostic relevance. Cancer Genome Atlas (TCGA) ECs dataset (<i>n</i> = 589) was also interrogated. The TCGA dataset further confirmed changes in <i>DKC1</i> expression in EC with prognostic significance. Transient dyskerin overexpression had a negative effect on EC cell proliferation. Our data demonstrates a role for dyskerin in normal endometrium for the first time and confirms aberrant expression with possible prognostic relevance in EC. Interventions aimed at modulating dyskerin levels may provide novel therapeutic options in EC. |
| first_indexed | 2024-03-09T04:58:04Z |
| format | Article |
| id | doaj.art-5ac1e1e18b134d0caf2f5df7849966e3 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T04:58:04Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5ac1e1e18b134d0caf2f5df7849966e32023-12-03T13:02:46ZengMDPI AGCancers2072-66942021-01-0113227310.3390/cancers13020273Aberrant Dyskerin Expression Is Related to Proliferation and Poor Survival in Endometrial CancerRafah Alnafakh0Gabriele Saretzki1Angela Midgley2James Flynn3Areege M. Kamal4Lucy Dobson5Purushothaman Natarajan6Helen Stringfellow7Pierre Martin-Hirsch8Shandya B. DeCruze9Sarah E. Coupland10Dharani K. Hapangama11Liverpool Women’s Hospital NHS Foundation Trust, Member of Liverpool Health Partners, Liverpool L8 7SS, UKBiosciences Institute, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne NE4 5PL, UKExperimental Arthritis Treatment Centre for Children, Institute in the Park, Department of Women’s and Children’s Health, University of Liverpool, Liverpool L12 2AP, UKIllumina Inc., San Diego, CA 92122, USADepartment of Women’s and Children’s Health, Institute of Life Course and Medical Sciences, University of Liverpool, Member of Liverpool Health Partners, Liverpool L8 7SS, UKLiverpool Women’s Hospital NHS Foundation Trust, Member of Liverpool Health Partners, Liverpool L8 7SS, UKLiverpool Women’s Hospital NHS Foundation Trust, Member of Liverpool Health Partners, Liverpool L8 7SS, UKLancashire Teaching Hospital NHS Trust, Preston PR2 9HT, UKLancashire Teaching Hospital NHS Trust, Preston PR2 9HT, UKLiverpool Women’s Hospital NHS Foundation Trust, Member of Liverpool Health Partners, Liverpool L8 7SS, UKMolecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L7 8TX, UKLiverpool Women’s Hospital NHS Foundation Trust, Member of Liverpool Health Partners, Liverpool L8 7SS, UKDyskerin is a core-component of the telomerase holo-enzyme, which elongates telomeres. Telomerase is involved in endometrial epithelial cell proliferation. Most endometrial cancers (ECs) have high telomerase activity; however, dyskerin expression in human healthy endometrium or in endometrial pathologies has not been investigated yet. We aimed to examine the expression, prognostic relevance, and functional role of dyskerin in human EC. Endometrial samples from a cohort of 175 women were examined with immunohistochemistry, immunoblotting, and qPCR. The EC cells were transfected with Myc-DDK-DKC1 plasmid and the effect of dyskerin overexpression on EC cell proliferation was assessed by flow cytometry. Human endometrium expresses dyskerin (<i>DKC1</i>) and dyskerin protein levels are significantly reduced in ECs when compared with healthy postmenopausal endometrium. Low dyskerin immunoscores were potentially associated with worse outcomes, suggesting a possible prognostic relevance. Cancer Genome Atlas (TCGA) ECs dataset (<i>n</i> = 589) was also interrogated. The TCGA dataset further confirmed changes in <i>DKC1</i> expression in EC with prognostic significance. Transient dyskerin overexpression had a negative effect on EC cell proliferation. Our data demonstrates a role for dyskerin in normal endometrium for the first time and confirms aberrant expression with possible prognostic relevance in EC. Interventions aimed at modulating dyskerin levels may provide novel therapeutic options in EC.https://www.mdpi.com/2072-6694/13/2/273dyskerin<i>DKC1</i>endometrial cancertelomeraseproliferationtelomeres |
| spellingShingle | Rafah Alnafakh Gabriele Saretzki Angela Midgley James Flynn Areege M. Kamal Lucy Dobson Purushothaman Natarajan Helen Stringfellow Pierre Martin-Hirsch Shandya B. DeCruze Sarah E. Coupland Dharani K. Hapangama Aberrant Dyskerin Expression Is Related to Proliferation and Poor Survival in Endometrial Cancer Cancers dyskerin <i>DKC1</i> endometrial cancer telomerase proliferation telomeres |
| title | Aberrant Dyskerin Expression Is Related to Proliferation and Poor Survival in Endometrial Cancer |
| title_full | Aberrant Dyskerin Expression Is Related to Proliferation and Poor Survival in Endometrial Cancer |
| title_fullStr | Aberrant Dyskerin Expression Is Related to Proliferation and Poor Survival in Endometrial Cancer |
| title_full_unstemmed | Aberrant Dyskerin Expression Is Related to Proliferation and Poor Survival in Endometrial Cancer |
| title_short | Aberrant Dyskerin Expression Is Related to Proliferation and Poor Survival in Endometrial Cancer |
| title_sort | aberrant dyskerin expression is related to proliferation and poor survival in endometrial cancer |
| topic | dyskerin <i>DKC1</i> endometrial cancer telomerase proliferation telomeres |
| url | https://www.mdpi.com/2072-6694/13/2/273 |
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