Cargando…
Robust expression of LINE-1 retrotransposon encoded proteins in oral squamous cell carcinoma
BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) results from a series of genetic alteration in squamous cells. This particular type of cancer considers one of the most aggressive malignancies to control because of its frequent local invasions to the regional lymph node. Although several biomarkers h...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161598/ https://www.ncbi.nlm.nih.gov/pubmed/34044801 http://dx.doi.org/10.1186/s12885-021-08174-z |
_version_ | 1783700540748726272 |
---|---|
author | Mukherjee, Koel Sur, Debpali Singh, Abhijeet Rai, Sandhya Das, Neeladrisingha Sekar, Rakshanya Narindi, Srinu Dhingra, Vandana Kumar Jat, Bhinyaram Balraam, K. V. Vinu Agarwal, Satya Prakash Mandal, Prabhat Kumar |
author_facet | Mukherjee, Koel Sur, Debpali Singh, Abhijeet Rai, Sandhya Das, Neeladrisingha Sekar, Rakshanya Narindi, Srinu Dhingra, Vandana Kumar Jat, Bhinyaram Balraam, K. V. Vinu Agarwal, Satya Prakash Mandal, Prabhat Kumar |
author_sort | Mukherjee, Koel |
collection | PubMed |
description | BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) results from a series of genetic alteration in squamous cells. This particular type of cancer considers one of the most aggressive malignancies to control because of its frequent local invasions to the regional lymph node. Although several biomarkers have been reported, the key marker used to predict the behavior of the disease is largely unknown. Here we report Long INterpersed Element-1 (LINE1 or L1) retrotransposon activity in post-operative oral cancer samples. L1 is the only active retrotransposon occupying around 17% of the human genome with an estimated 500,000 copies. An active L1 encodes two proteins (L1ORF1p and L1ORF2p); both of which are critical in the process of retrotransposition. Several studies report that the L1 retrotransposon is highly active in many cancers. L1 activity is generally determined by assaying L1ORF1p because of its high expression and availability of the antibody. However, due to its lower expression and unavailability of a robust antibody, detection of L1ORF2p has been limited. L1ORF2p is the crucial protein in the process of retrotransposition as it provides endonuclease and reverse transcriptase (RT) activity. METHODS: Immunohistochemistry and Western blotting were performed on the post-operative oral cancer samples and murine tissues. RESULTS: Using in house novel antibodies against both the L1 proteins (L1ORF1p and L1ORF2p), we found L1 retrotransposon is extremely active in post-operative oral cancer tissues. Here, we report a novel human L1ORF2p antibody generated using an 80-amino-acid stretch from the RT domain, which is highly conserved among different species. The antibody detects significant L1ORF2p expression in human oral squamous cell carcinoma (OSCC) samples and murine germ tissues. CONCLUSIONS: We report exceptionally high L1ORF1p and L1ORF2p expression in post-operative oral cancer samples. The novel L1ORF2p antibody reported in this study will serve as a useful tool to understand why L1 activity is deregulated in OSCC and how it contributes to the progression of this particular cancer. Cross-species reactivity of L1ORF2p antibody due to the conserved epitope will be useful to study the retrotransposon biology in mice and rat germ tissues. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08174-z. |
format | Online Article Text |
id | pubmed-8161598 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-81615982021-06-01 Robust expression of LINE-1 retrotransposon encoded proteins in oral squamous cell carcinoma Mukherjee, Koel Sur, Debpali Singh, Abhijeet Rai, Sandhya Das, Neeladrisingha Sekar, Rakshanya Narindi, Srinu Dhingra, Vandana Kumar Jat, Bhinyaram Balraam, K. V. Vinu Agarwal, Satya Prakash Mandal, Prabhat Kumar BMC Cancer Research BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) results from a series of genetic alteration in squamous cells. This particular type of cancer considers one of the most aggressive malignancies to control because of its frequent local invasions to the regional lymph node. Although several biomarkers have been reported, the key marker used to predict the behavior of the disease is largely unknown. Here we report Long INterpersed Element-1 (LINE1 or L1) retrotransposon activity in post-operative oral cancer samples. L1 is the only active retrotransposon occupying around 17% of the human genome with an estimated 500,000 copies. An active L1 encodes two proteins (L1ORF1p and L1ORF2p); both of which are critical in the process of retrotransposition. Several studies report that the L1 retrotransposon is highly active in many cancers. L1 activity is generally determined by assaying L1ORF1p because of its high expression and availability of the antibody. However, due to its lower expression and unavailability of a robust antibody, detection of L1ORF2p has been limited. L1ORF2p is the crucial protein in the process of retrotransposition as it provides endonuclease and reverse transcriptase (RT) activity. METHODS: Immunohistochemistry and Western blotting were performed on the post-operative oral cancer samples and murine tissues. RESULTS: Using in house novel antibodies against both the L1 proteins (L1ORF1p and L1ORF2p), we found L1 retrotransposon is extremely active in post-operative oral cancer tissues. Here, we report a novel human L1ORF2p antibody generated using an 80-amino-acid stretch from the RT domain, which is highly conserved among different species. The antibody detects significant L1ORF2p expression in human oral squamous cell carcinoma (OSCC) samples and murine germ tissues. CONCLUSIONS: We report exceptionally high L1ORF1p and L1ORF2p expression in post-operative oral cancer samples. The novel L1ORF2p antibody reported in this study will serve as a useful tool to understand why L1 activity is deregulated in OSCC and how it contributes to the progression of this particular cancer. Cross-species reactivity of L1ORF2p antibody due to the conserved epitope will be useful to study the retrotransposon biology in mice and rat germ tissues. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08174-z. BioMed Central 2021-05-27 /pmc/articles/PMC8161598/ /pubmed/34044801 http://dx.doi.org/10.1186/s12885-021-08174-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Mukherjee, Koel Sur, Debpali Singh, Abhijeet Rai, Sandhya Das, Neeladrisingha Sekar, Rakshanya Narindi, Srinu Dhingra, Vandana Kumar Jat, Bhinyaram Balraam, K. V. Vinu Agarwal, Satya Prakash Mandal, Prabhat Kumar Robust expression of LINE-1 retrotransposon encoded proteins in oral squamous cell carcinoma |
title | Robust expression of LINE-1 retrotransposon encoded proteins in oral squamous cell carcinoma |
title_full | Robust expression of LINE-1 retrotransposon encoded proteins in oral squamous cell carcinoma |
title_fullStr | Robust expression of LINE-1 retrotransposon encoded proteins in oral squamous cell carcinoma |
title_full_unstemmed | Robust expression of LINE-1 retrotransposon encoded proteins in oral squamous cell carcinoma |
title_short | Robust expression of LINE-1 retrotransposon encoded proteins in oral squamous cell carcinoma |
title_sort | robust expression of line-1 retrotransposon encoded proteins in oral squamous cell carcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161598/ https://www.ncbi.nlm.nih.gov/pubmed/34044801 http://dx.doi.org/10.1186/s12885-021-08174-z |
work_keys_str_mv | AT mukherjeekoel robustexpressionofline1retrotransposonencodedproteinsinoralsquamouscellcarcinoma AT surdebpali robustexpressionofline1retrotransposonencodedproteinsinoralsquamouscellcarcinoma AT singhabhijeet robustexpressionofline1retrotransposonencodedproteinsinoralsquamouscellcarcinoma AT raisandhya robustexpressionofline1retrotransposonencodedproteinsinoralsquamouscellcarcinoma AT dasneeladrisingha robustexpressionofline1retrotransposonencodedproteinsinoralsquamouscellcarcinoma AT sekarrakshanya robustexpressionofline1retrotransposonencodedproteinsinoralsquamouscellcarcinoma AT narindisrinu robustexpressionofline1retrotransposonencodedproteinsinoralsquamouscellcarcinoma AT dhingravandanakumar robustexpressionofline1retrotransposonencodedproteinsinoralsquamouscellcarcinoma AT jatbhinyaram robustexpressionofline1retrotransposonencodedproteinsinoralsquamouscellcarcinoma AT balraamkvvinu robustexpressionofline1retrotransposonencodedproteinsinoralsquamouscellcarcinoma AT agarwalsatyaprakash robustexpressionofline1retrotransposonencodedproteinsinoralsquamouscellcarcinoma AT mandalprabhatkumar robustexpressionofline1retrotransposonencodedproteinsinoralsquamouscellcarcinoma |