Telomere Elongation and Mismatch Repair Deficiency Distinguish MSI Colorectal Cancer Cell Lines

Rajasekhar Moka; Shreya Upadhya

doi:doi:10.11648/j.crj.20251302.11

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Telomere Elongation and Mismatch Repair Deficiency Distinguish MSI Colorectal Cancer Cell Lines

Rajasekhar Moka^*

, Shreya Upadhya

Published in Cancer Research Journal (Volume 13, Issue 2)

Received: 17 April 2025 Accepted: 29 April 2025 Published: 29 May 2025

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Abstract

Microsatellite instability (MSI) is a hallmark of mismatch repair (MMR) deficiency and characterizes a distinct subset of colorectal cancers (CRC). In parallel, telomere length dynamics have emerged as important contributors to genomic stability and tumorigenesis. However, the relationship between MSI status, MMR protein expression, and telomere maintenance remains poorly defined. This study aimed to investigate the association between MSI status and telomere length in CRC cell lines and to evaluate the expression of key MMR proteins (MLH1, MSH2, MSH6, PMS2) to elucidate molecular differences between MSI and microsatellite stable (MSS) phenotypes. A panel of CRC cell lines with known MSI and MSS statuses was used. Telomere length was quantified using real-time quantitative PCR (qPCR) based on the T/S ratio method. MSI status was confirmed via PCR using mononucleotide repeat markers. Western blotting was performed to assess protein expressions of MLH1, MSH2, MSH6, and PMS2. β-actin served as a loading control. qPCR analysis revealed that MSI cell lines exhibited significantly longer telomeres compared to MSS lines (P < 0.05). Western blot results showed reduced or absent expression of MLH1 and PMS2 in MSI cell lines, confirming MMR deficiency. In contrast, MSS cell lines maintained normal expression of all tested MMR proteins. These findings suggest a link between defective MMR function and altered telomere dynamics in MSI-CRC. MSI CRC cell lines exhibit telomere elongation and loss of key MMR proteins, highlighting distinct molecular features compared to MSS counterparts. These insights may inform future strategies for personalized CRC diagnostics and therapeutics, particularly in the context of telomere-targeted or immunomodulatory treatments.

Published in	Cancer Research Journal (Volume 13, Issue 2)
DOI	10.11648/j.crj.20251302.11
Page(s)	23-29
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2025. Published by Science Publishing Group

Keywords

Colorectal Cancer, Telomere Length, Microsatellite Instability, Mismatch Repair Pathway, MMqPCR, Western Blotting, HRM Analysis

References

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APA Style

Moka, R., Upadhya, S. (2025). Telomere Elongation and Mismatch Repair Deficiency Distinguish MSI Colorectal Cancer Cell Lines. Cancer Research Journal, 13(2), 23-29. https://doi.org/10.11648/j.crj.20251302.11

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ACS Style

Moka, R.; Upadhya, S. Telomere Elongation and Mismatch Repair Deficiency Distinguish MSI Colorectal Cancer Cell Lines. Cancer Res. J. 2025, 13(2), 23-29. doi: 10.11648/j.crj.20251302.11

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AMA Style

Moka R, Upadhya S. Telomere Elongation and Mismatch Repair Deficiency Distinguish MSI Colorectal Cancer Cell Lines. Cancer Res J. 2025;13(2):23-29. doi: 10.11648/j.crj.20251302.11

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@article{10.11648/j.crj.20251302.11,
  author = {Rajasekhar Moka and Shreya Upadhya},
  title = {Telomere Elongation and Mismatch Repair Deficiency Distinguish MSI Colorectal Cancer Cell Lines
},
  journal = {Cancer Research Journal},
  volume = {13},
  number = {2},
  pages = {23-29},
  doi = {10.11648/j.crj.20251302.11},
  url = {https://doi.org/10.11648/j.crj.20251302.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20251302.11},
  abstract = {Microsatellite instability (MSI) is a hallmark of mismatch repair (MMR) deficiency and characterizes a distinct subset of colorectal cancers (CRC). In parallel, telomere length dynamics have emerged as important contributors to genomic stability and tumorigenesis. However, the relationship between MSI status, MMR protein expression, and telomere maintenance remains poorly defined. This study aimed to investigate the association between MSI status and telomere length in CRC cell lines and to evaluate the expression of key MMR proteins (MLH1, MSH2, MSH6, PMS2) to elucidate molecular differences between MSI and microsatellite stable (MSS) phenotypes. A panel of CRC cell lines with known MSI and MSS statuses was used. Telomere length was quantified using real-time quantitative PCR (qPCR) based on the T/S ratio method. MSI status was confirmed via PCR using mononucleotide repeat markers. Western blotting was performed to assess protein expressions of MLH1, MSH2, MSH6, and PMS2. β-actin served as a loading control. qPCR analysis revealed that MSI cell lines exhibited significantly longer telomeres compared to MSS lines (P < 0.05). Western blot results showed reduced or absent expression of MLH1 and PMS2 in MSI cell lines, confirming MMR deficiency. In contrast, MSS cell lines maintained normal expression of all tested MMR proteins. These findings suggest a link between defective MMR function and altered telomere dynamics in MSI-CRC. MSI CRC cell lines exhibit telomere elongation and loss of key MMR proteins, highlighting distinct molecular features compared to MSS counterparts. These insights may inform future strategies for personalized CRC diagnostics and therapeutics, particularly in the context of telomere-targeted or immunomodulatory treatments.
},
 year = {2025}
}

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TY - JOUR
T1 - Telomere Elongation and Mismatch Repair Deficiency Distinguish MSI Colorectal Cancer Cell Lines

AU - Rajasekhar Moka
AU - Shreya Upadhya
Y1 - 2025/05/29
PY - 2025
N1 - https://doi.org/10.11648/j.crj.20251302.11
DO - 10.11648/j.crj.20251302.11
T2 - Cancer Research Journal
JF - Cancer Research Journal
JO - Cancer Research Journal
SP - 23
EP - 29
PB - Science Publishing Group
SN - 2330-8214
UR - https://doi.org/10.11648/j.crj.20251302.11
AB - Microsatellite instability (MSI) is a hallmark of mismatch repair (MMR) deficiency and characterizes a distinct subset of colorectal cancers (CRC). In parallel, telomere length dynamics have emerged as important contributors to genomic stability and tumorigenesis. However, the relationship between MSI status, MMR protein expression, and telomere maintenance remains poorly defined. This study aimed to investigate the association between MSI status and telomere length in CRC cell lines and to evaluate the expression of key MMR proteins (MLH1, MSH2, MSH6, PMS2) to elucidate molecular differences between MSI and microsatellite stable (MSS) phenotypes. A panel of CRC cell lines with known MSI and MSS statuses was used. Telomere length was quantified using real-time quantitative PCR (qPCR) based on the T/S ratio method. MSI status was confirmed via PCR using mononucleotide repeat markers. Western blotting was performed to assess protein expressions of MLH1, MSH2, MSH6, and PMS2. β-actin served as a loading control. qPCR analysis revealed that MSI cell lines exhibited significantly longer telomeres compared to MSS lines (P < 0.05). Western blot results showed reduced or absent expression of MLH1 and PMS2 in MSI cell lines, confirming MMR deficiency. In contrast, MSS cell lines maintained normal expression of all tested MMR proteins. These findings suggest a link between defective MMR function and altered telomere dynamics in MSI-CRC. MSI CRC cell lines exhibit telomere elongation and loss of key MMR proteins, highlighting distinct molecular features compared to MSS counterparts. These insights may inform future strategies for personalized CRC diagnostics and therapeutics, particularly in the context of telomere-targeted or immunomodulatory treatments.

VL - 13
IS - 2
ER -

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Author Information

Rajasekhar Moka

Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India

Contact Email

http://orcid.org/0000-0002-5578-8806
Shreya Upadhya

Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India

http://orcid.org/0009-0006-9415-3009

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APA Style

Moka, R., Upadhya, S. (2025). Telomere Elongation and Mismatch Repair Deficiency Distinguish MSI Colorectal Cancer Cell Lines. Cancer Research Journal, 13(2), 23-29. https://doi.org/10.11648/j.crj.20251302.11

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ACS Style

Moka, R.; Upadhya, S. Telomere Elongation and Mismatch Repair Deficiency Distinguish MSI Colorectal Cancer Cell Lines. Cancer Res. J. 2025, 13(2), 23-29. doi: 10.11648/j.crj.20251302.11

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AMA Style

Moka R, Upadhya S. Telomere Elongation and Mismatch Repair Deficiency Distinguish MSI Colorectal Cancer Cell Lines. Cancer Res J. 2025;13(2):23-29. doi: 10.11648/j.crj.20251302.11

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@article{10.11648/j.crj.20251302.11,
  author = {Rajasekhar Moka and Shreya Upadhya},
  title = {Telomere Elongation and Mismatch Repair Deficiency Distinguish MSI Colorectal Cancer Cell Lines
},
  journal = {Cancer Research Journal},
  volume = {13},
  number = {2},
  pages = {23-29},
  doi = {10.11648/j.crj.20251302.11},
  url = {https://doi.org/10.11648/j.crj.20251302.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20251302.11},
  abstract = {Microsatellite instability (MSI) is a hallmark of mismatch repair (MMR) deficiency and characterizes a distinct subset of colorectal cancers (CRC). In parallel, telomere length dynamics have emerged as important contributors to genomic stability and tumorigenesis. However, the relationship between MSI status, MMR protein expression, and telomere maintenance remains poorly defined. This study aimed to investigate the association between MSI status and telomere length in CRC cell lines and to evaluate the expression of key MMR proteins (MLH1, MSH2, MSH6, PMS2) to elucidate molecular differences between MSI and microsatellite stable (MSS) phenotypes. A panel of CRC cell lines with known MSI and MSS statuses was used. Telomere length was quantified using real-time quantitative PCR (qPCR) based on the T/S ratio method. MSI status was confirmed via PCR using mononucleotide repeat markers. Western blotting was performed to assess protein expressions of MLH1, MSH2, MSH6, and PMS2. β-actin served as a loading control. qPCR analysis revealed that MSI cell lines exhibited significantly longer telomeres compared to MSS lines (P < 0.05). Western blot results showed reduced or absent expression of MLH1 and PMS2 in MSI cell lines, confirming MMR deficiency. In contrast, MSS cell lines maintained normal expression of all tested MMR proteins. These findings suggest a link between defective MMR function and altered telomere dynamics in MSI-CRC. MSI CRC cell lines exhibit telomere elongation and loss of key MMR proteins, highlighting distinct molecular features compared to MSS counterparts. These insights may inform future strategies for personalized CRC diagnostics and therapeutics, particularly in the context of telomere-targeted or immunomodulatory treatments.
},
 year = {2025}
}

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TY - JOUR
T1 - Telomere Elongation and Mismatch Repair Deficiency Distinguish MSI Colorectal Cancer Cell Lines

VL - 13
IS - 2
ER -

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