The Ultraviolet Irradiation of Keratinocytes Induces Ectopic Expression of LINE-1 Retrotransposon Machinery and Leads to Cellular Senescence
Retrotransposons have played an important role in evolution through their transposable activity. The largest and the only currently active human group of mobile DNAs are the <i>LINE-1</i> retrotransposons. The ectopic expression of <i>LINE-1</i> has been correlated with genom...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/11/3017 |
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| author | Fadi Touma Marine Lambert Amelia Martínez Villarreal Jennifer Gantchev Brandon Ramchatesingh Ivan V. Litvinov |
| author_facet | Fadi Touma Marine Lambert Amelia Martínez Villarreal Jennifer Gantchev Brandon Ramchatesingh Ivan V. Litvinov |
| author_sort | Fadi Touma |
| collection | DOAJ |
| description | Retrotransposons have played an important role in evolution through their transposable activity. The largest and the only currently active human group of mobile DNAs are the <i>LINE-1</i> retrotransposons. The ectopic expression of <i>LINE-1</i> has been correlated with genomic instability. Narrow-band ultraviolet B (NB-UVB) and broad-band ultraviolet B (BB-UVB) phototherapy is commonly used for the treatment of dermatological diseases. UVB exposure is carcinogenic and can lead, in keratinocytes, to genomic instability. We hypothesize that <i>LINE-1</i> reactivation occurs at a high rate in response to UVB exposure on the skin, which significantly contributes to genomic instability and DNA damage leading to cellular senescence and photoaging. Immortalized N/TERT1 and HaCaT human keratinocyte cell lines were irradiated in vitro with either NB-UVB or BB-UVB. Using immunofluorescence and Western blotting, we confirmed UVB-induced protein expression of LINE-1. Using RT-qPCR, we measured the mRNA expression of <i>LINE-1</i> and senescence markers that were upregulated after several NB-UVB exposures. Selected miRNAs that are known to bind <i>LINE-1</i> mRNA were measured using RT-qPCR, and the expression of <i>miR-16</i> was downregulated with UVB exposure. Our findings demonstrate that UVB irradiation induces <i>LINE-1</i> reactivation and DNA damage in normal keratinocytes along with the associated upregulation of cellular senescence markers and change in <i>miR-16</i> expression. |
| first_indexed | 2024-03-09T17:00:02Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-09T17:00:02Z |
| publishDate | 2023-11-01 |
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| series | Biomedicines |
| spelling | doaj.art-a566e2adac2f4caf826ba5d7aa87b4ed2023-11-24T14:31:10ZengMDPI AGBiomedicines2227-90592023-11-011111301710.3390/biomedicines11113017The Ultraviolet Irradiation of Keratinocytes Induces Ectopic Expression of LINE-1 Retrotransposon Machinery and Leads to Cellular SenescenceFadi Touma0Marine Lambert1Amelia Martínez Villarreal2Jennifer Gantchev3Brandon Ramchatesingh4Ivan V. Litvinov5Research Institute, McGill University Health Centre, McGill University, Montreal, QC H4A 3J1, CanadaResearch Institute, McGill University Health Centre, McGill University, Montreal, QC H4A 3J1, CanadaResearch Institute, McGill University Health Centre, McGill University, Montreal, QC H4A 3J1, CanadaResearch Institute, McGill University Health Centre, McGill University, Montreal, QC H4A 3J1, CanadaResearch Institute, McGill University Health Centre, McGill University, Montreal, QC H4A 3J1, CanadaResearch Institute, McGill University Health Centre, McGill University, Montreal, QC H4A 3J1, CanadaRetrotransposons have played an important role in evolution through their transposable activity. The largest and the only currently active human group of mobile DNAs are the <i>LINE-1</i> retrotransposons. The ectopic expression of <i>LINE-1</i> has been correlated with genomic instability. Narrow-band ultraviolet B (NB-UVB) and broad-band ultraviolet B (BB-UVB) phototherapy is commonly used for the treatment of dermatological diseases. UVB exposure is carcinogenic and can lead, in keratinocytes, to genomic instability. We hypothesize that <i>LINE-1</i> reactivation occurs at a high rate in response to UVB exposure on the skin, which significantly contributes to genomic instability and DNA damage leading to cellular senescence and photoaging. Immortalized N/TERT1 and HaCaT human keratinocyte cell lines were irradiated in vitro with either NB-UVB or BB-UVB. Using immunofluorescence and Western blotting, we confirmed UVB-induced protein expression of LINE-1. Using RT-qPCR, we measured the mRNA expression of <i>LINE-1</i> and senescence markers that were upregulated after several NB-UVB exposures. Selected miRNAs that are known to bind <i>LINE-1</i> mRNA were measured using RT-qPCR, and the expression of <i>miR-16</i> was downregulated with UVB exposure. Our findings demonstrate that UVB irradiation induces <i>LINE-1</i> reactivation and DNA damage in normal keratinocytes along with the associated upregulation of cellular senescence markers and change in <i>miR-16</i> expression.https://www.mdpi.com/2227-9059/11/11/3017long interspersed nucleotide element-1 (LINE-1)phototherapykeratinocytesBB-UVBNB-UVBgenomic instability |
| spellingShingle | Fadi Touma Marine Lambert Amelia Martínez Villarreal Jennifer Gantchev Brandon Ramchatesingh Ivan V. Litvinov The Ultraviolet Irradiation of Keratinocytes Induces Ectopic Expression of LINE-1 Retrotransposon Machinery and Leads to Cellular Senescence Biomedicines long interspersed nucleotide element-1 (LINE-1) phototherapy keratinocytes BB-UVB NB-UVB genomic instability |
| title | The Ultraviolet Irradiation of Keratinocytes Induces Ectopic Expression of LINE-1 Retrotransposon Machinery and Leads to Cellular Senescence |
| title_full | The Ultraviolet Irradiation of Keratinocytes Induces Ectopic Expression of LINE-1 Retrotransposon Machinery and Leads to Cellular Senescence |
| title_fullStr | The Ultraviolet Irradiation of Keratinocytes Induces Ectopic Expression of LINE-1 Retrotransposon Machinery and Leads to Cellular Senescence |
| title_full_unstemmed | The Ultraviolet Irradiation of Keratinocytes Induces Ectopic Expression of LINE-1 Retrotransposon Machinery and Leads to Cellular Senescence |
| title_short | The Ultraviolet Irradiation of Keratinocytes Induces Ectopic Expression of LINE-1 Retrotransposon Machinery and Leads to Cellular Senescence |
| title_sort | ultraviolet irradiation of keratinocytes induces ectopic expression of line 1 retrotransposon machinery and leads to cellular senescence |
| topic | long interspersed nucleotide element-1 (LINE-1) phototherapy keratinocytes BB-UVB NB-UVB genomic instability |
| url | https://www.mdpi.com/2227-9059/11/11/3017 |
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