Literature DB >> 34044801

Robust expression of LINE-1 retrotransposon encoded proteins in oral squamous cell carcinoma.

Debpali Sur1, Abhijeet Singh2, Koel Mukherjee1, Sandhya Rai1, Neeladrisingha Das1, Rakshanya Sekar3, Srinu Narindi4, Vandana Kumar Dhingra2, Bhinyaram Jat2, K V Vinu Balraam4, Satya Prakash Agarwal2, Prabhat Kumar Mandal5.   

Abstract

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.

Entities:  

Keywords:  Cancer and L1 retrotransposon; L1 retrotransposon; L1ORF1p antibody; L1ORF2p antibody; OSCC and L1 retrotransposon

Year:  2021        PMID: 34044801     DOI: 10.1186/s12885-021-08174-z

Source DB:  PubMed          Journal:  BMC Cancer        ISSN: 1471-2407            Impact factor:   4.430


  48 in total

1.  Hot L1s account for the bulk of retrotransposition in the human population.

Authors:  Brook Brouha; Joshua Schustak; Richard M Badge; Sheila Lutz-Prigge; Alexander H Farley; John V Moran; Haig H Kazazian
Journal:  Proc Natl Acad Sci U S A       Date:  2003-04-07       Impact factor: 11.205

2.  Retrotransposition of marked SVA elements by human L1s in cultured cells.

Authors:  Dustin C Hancks; John L Goodier; Prabhat K Mandal; Ling E Cheung; Haig H Kazazian
Journal:  Hum Mol Genet       Date:  2011-06-02       Impact factor: 6.150

3.  Identification, characterization, and cell specificity of a human LINE-1 promoter.

Authors:  G D Swergold
Journal:  Mol Cell Biol       Date:  1990-12       Impact factor: 4.272

4.  SnapShot: Vertebrate transposons.

Authors:  Prabhat K Mandal; Haig H Kazazian
Journal:  Cell       Date:  2008-10-03       Impact factor: 41.582

5.  Human LINE retrotransposons generate processed pseudogenes.

Authors:  C Esnault; J Maestre; T Heidmann
Journal:  Nat Genet       Date:  2000-04       Impact factor: 38.330

Review 6.  Active transposition in genomes.

Authors:  Cheng Ran Lisa Huang; Kathleen H Burns; Jef D Boeke
Journal:  Annu Rev Genet       Date:  2012       Impact factor: 16.830

Review 7.  Mobile DNA in Health and Disease.

Authors:  Haig H Kazazian; John V Moran
Journal:  N Engl J Med       Date:  2017-07-27       Impact factor: 91.245

8.  LINE-mediated retrotransposition of marked Alu sequences.

Authors:  Marie Dewannieux; Cécile Esnault; Thierry Heidmann
Journal:  Nat Genet       Date:  2003-08-03       Impact factor: 38.330

9.  The non-autonomous retrotransposon SVA is trans-mobilized by the human LINE-1 protein machinery.

Authors:  Julija Raiz; Annette Damert; Sergiu Chira; Ulrike Held; Sabine Klawitter; Matthias Hamdorf; Johannes Löwer; Wolf H Strätling; Roswitha Löwer; Gerald G Schumann
Journal:  Nucleic Acids Res       Date:  2011-11-03       Impact factor: 16.971

10.  Origin of the human L1 elements: proposed progenitor genes deduced from a consensus DNA sequence.

Authors:  A F Scott; B J Schmeckpeper; M Abdelrazik; C T Comey; B O'Hara; J P Rossiter; T Cooley; P Heath; K D Smith; L Margolet
Journal:  Genomics       Date:  1987-10       Impact factor: 5.736

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