The expression of telomere-related proteins and DNA damage response and their association with telomere length in colorectal cancer in Saudi patients.
BACKGROUND:Colorectal cancer is the leading cause of cancer-related deaths in Saudi Arabia. Cancer has a multifactorial nature and can be described as a disease of altered gene expression. The profiling of gene expression has been used to identify cancer subtypes and to predict patients' respon...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5988329?pdf=render |
| _version_ | 1818537980525019136 |
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| author | Ftoon Aljarbou Nourah Almousa Mohammad Bazzi Sooad Aldaihan Mohammed Alanazi Othman Alharbi Majid Almadi Abdulrahman M Aljebreen Nahla Ali Azzam Maha Arafa Abeer Aldbass Jilani Shaik Shaheerah Alasirri Arjumand Warsy Abdullah Alamri Narasimha Reddy Parine Ghadah Alamro |
| author_facet | Ftoon Aljarbou Nourah Almousa Mohammad Bazzi Sooad Aldaihan Mohammed Alanazi Othman Alharbi Majid Almadi Abdulrahman M Aljebreen Nahla Ali Azzam Maha Arafa Abeer Aldbass Jilani Shaik Shaheerah Alasirri Arjumand Warsy Abdullah Alamri Narasimha Reddy Parine Ghadah Alamro |
| author_sort | Ftoon Aljarbou |
| collection | DOAJ |
| description | BACKGROUND:Colorectal cancer is the leading cause of cancer-related deaths in Saudi Arabia. Cancer has a multifactorial nature and can be described as a disease of altered gene expression. The profiling of gene expression has been used to identify cancer subtypes and to predict patients' responsiveness. Telomere-associated proteins that regulate telomere biology are essential molecules in cancer development. Thus, the present study examined their contributions to colorectal cancer progression in Saudi patients. METHODS:The expression of hTERT, TRF1, TRF2, POT1, ATR, ATM, Chk1 and Chk2 were measured via real-time PCR in matched cancerous and adjacent tissues of CRC patients. The protein level of hTERT, TRF1, TRF2, ATR, ATM, Chk1 and Chk2 were measured using immunohistochemistry. A region of hTERT core promoter was sequenced via Sanger sequencing. Methylation of CTCF binding site was examined via methylation-specific PCR. Finally, the length of telomere was estimated using q-PCR. RESULTS:Our results showed that POT1, ATR, Chk1 and Chk2 show increased expression in CRC relative to the adjacent mucosa. The expression levels of each gene were associated with clinicopathological characteristics of patients with CRC. There was a positive correlation between the age of the patients and hTERT expression. Regarding tumor site, telomere length, ATR, ATM and Chk1 were shown to be altered. No somatic mutation was detected in hTERT core promoter, and no differences in methylation patterns at CTCF binding site in the promoter between normal and cancer tissues. CONCLUSION:Analysis of targeted genes expression in colorectal cancer based on the clinical variables revealed that tumor location and age could have a role in gene expression and telomere length variations and this could be taken under consideration during CRC diagnosis and therapy. Other epigenetic mechanisms could influence hTERT expression in cancers. Our findings warrant further validation through experiments involving a larger number of patients. |
| first_indexed | 2024-12-11T18:57:42Z |
| format | Article |
| id | doaj.art-3cd2750905b540b09d0be1040c8eb89f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T18:57:42Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3cd2750905b540b09d0be1040c8eb89f2022-12-22T00:54:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019715410.1371/journal.pone.0197154The expression of telomere-related proteins and DNA damage response and their association with telomere length in colorectal cancer in Saudi patients.Ftoon AljarbouNourah AlmousaMohammad BazziSooad AldaihanMohammed AlanaziOthman AlharbiMajid AlmadiAbdulrahman M AljebreenNahla Ali AzzamMaha ArafaAbeer AldbassJilani ShaikShaheerah AlasirriArjumand WarsyAbdullah AlamriNarasimha Reddy ParineGhadah AlamroBACKGROUND:Colorectal cancer is the leading cause of cancer-related deaths in Saudi Arabia. Cancer has a multifactorial nature and can be described as a disease of altered gene expression. The profiling of gene expression has been used to identify cancer subtypes and to predict patients' responsiveness. Telomere-associated proteins that regulate telomere biology are essential molecules in cancer development. Thus, the present study examined their contributions to colorectal cancer progression in Saudi patients. METHODS:The expression of hTERT, TRF1, TRF2, POT1, ATR, ATM, Chk1 and Chk2 were measured via real-time PCR in matched cancerous and adjacent tissues of CRC patients. The protein level of hTERT, TRF1, TRF2, ATR, ATM, Chk1 and Chk2 were measured using immunohistochemistry. A region of hTERT core promoter was sequenced via Sanger sequencing. Methylation of CTCF binding site was examined via methylation-specific PCR. Finally, the length of telomere was estimated using q-PCR. RESULTS:Our results showed that POT1, ATR, Chk1 and Chk2 show increased expression in CRC relative to the adjacent mucosa. The expression levels of each gene were associated with clinicopathological characteristics of patients with CRC. There was a positive correlation between the age of the patients and hTERT expression. Regarding tumor site, telomere length, ATR, ATM and Chk1 were shown to be altered. No somatic mutation was detected in hTERT core promoter, and no differences in methylation patterns at CTCF binding site in the promoter between normal and cancer tissues. CONCLUSION:Analysis of targeted genes expression in colorectal cancer based on the clinical variables revealed that tumor location and age could have a role in gene expression and telomere length variations and this could be taken under consideration during CRC diagnosis and therapy. Other epigenetic mechanisms could influence hTERT expression in cancers. Our findings warrant further validation through experiments involving a larger number of patients.http://europepmc.org/articles/PMC5988329?pdf=render |
| spellingShingle | Ftoon Aljarbou Nourah Almousa Mohammad Bazzi Sooad Aldaihan Mohammed Alanazi Othman Alharbi Majid Almadi Abdulrahman M Aljebreen Nahla Ali Azzam Maha Arafa Abeer Aldbass Jilani Shaik Shaheerah Alasirri Arjumand Warsy Abdullah Alamri Narasimha Reddy Parine Ghadah Alamro The expression of telomere-related proteins and DNA damage response and their association with telomere length in colorectal cancer in Saudi patients. PLoS ONE |
| title | The expression of telomere-related proteins and DNA damage response and their association with telomere length in colorectal cancer in Saudi patients. |
| title_full | The expression of telomere-related proteins and DNA damage response and their association with telomere length in colorectal cancer in Saudi patients. |
| title_fullStr | The expression of telomere-related proteins and DNA damage response and their association with telomere length in colorectal cancer in Saudi patients. |
| title_full_unstemmed | The expression of telomere-related proteins and DNA damage response and their association with telomere length in colorectal cancer in Saudi patients. |
| title_short | The expression of telomere-related proteins and DNA damage response and their association with telomere length in colorectal cancer in Saudi patients. |
| title_sort | expression of telomere related proteins and dna damage response and their association with telomere length in colorectal cancer in saudi patients |
| url | http://europepmc.org/articles/PMC5988329?pdf=render |
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