Endogenous Retroviral Elements in Human Development and Central Nervous System Embryonal Tumors
Human endogenous retroviruses (HERVs), which are critical to normal embryologic development and downregulated during normal maturation, have been implicated in a variety of cancers. Abnormal persistent production of HERVs has been suggested to play a role in oncogenesis and to confer stem cell prope...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Journal of Personalized Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4426/11/12/1332 |
| _version_ | 1797503132118286336 |
|---|---|
| author | Tara T. Doucet-O’Hare Jared S. Rosenblum Ashish H. Shah Mark R. Gilbert Zhengping Zhuang |
| author_facet | Tara T. Doucet-O’Hare Jared S. Rosenblum Ashish H. Shah Mark R. Gilbert Zhengping Zhuang |
| author_sort | Tara T. Doucet-O’Hare |
| collection | DOAJ |
| description | Human endogenous retroviruses (HERVs), which are critical to normal embryologic development and downregulated during normal maturation, have been implicated in a variety of cancers. Abnormal persistent production of HERVs has been suggested to play a role in oncogenesis and to confer stem cell properties to cells. We recently demonstrated that the most recently incorporated HERV element (HERV-K HML-2) has been associated with the pathogenesis of the embryonal atypical teratoid rhabdoid tumor (AT/RT), shifting our understanding of embryonal tumor development. HML-2 expression is vital for proper human development and its expression is suppressed via methylation or chromatin remodeling as cells differentiate. We previously found that dysfunctional chromatin remodeling due to loss of SMARCB1 expression induces HML-2 envelope (env) expression, impairing cellular differentiation and migration, and facilitating tumor growth in AT/RT. Epigenetic dysregulation in other embryonal tumors with concomitant expression of stem-cell markers may facilitate HML-2 expression. Future studies could utilize HML-2 as potential diagnostic criteria, use its expression as a treatment biomarker, and investigate the efficacy of therapies targeting cells with high HML-2 expression. |
| first_indexed | 2024-03-10T03:46:09Z |
| format | Article |
| id | doaj.art-acc2275954884907bae3c56850950c10 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T03:46:09Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-acc2275954884907bae3c56850950c102023-11-23T09:08:04ZengMDPI AGJournal of Personalized Medicine2075-44262021-12-011112133210.3390/jpm11121332Endogenous Retroviral Elements in Human Development and Central Nervous System Embryonal TumorsTara T. Doucet-O’Hare0Jared S. Rosenblum1Ashish H. Shah2Mark R. Gilbert3Zhengping Zhuang4National Cancer Institute, Center for Cancer Research, Neuro-Oncology Branch, Building 37, Room 1000, 37 Convent Drive, Bethesda, MD 20892, USANational Cancer Institute, Center for Cancer Research, Neuro-Oncology Branch, Building 37, Room 1000, 37 Convent Drive, Bethesda, MD 20892, USANational Institutes of Neurological Disorders and Stroke (NINDS), Surgical Neurology Branch, Bethesda, MD 20892, USANational Cancer Institute, Center for Cancer Research, Neuro-Oncology Branch, Building 37, Room 1000, 37 Convent Drive, Bethesda, MD 20892, USANational Cancer Institute, Center for Cancer Research, Neuro-Oncology Branch, Building 37, Room 1000, 37 Convent Drive, Bethesda, MD 20892, USAHuman endogenous retroviruses (HERVs), which are critical to normal embryologic development and downregulated during normal maturation, have been implicated in a variety of cancers. Abnormal persistent production of HERVs has been suggested to play a role in oncogenesis and to confer stem cell properties to cells. We recently demonstrated that the most recently incorporated HERV element (HERV-K HML-2) has been associated with the pathogenesis of the embryonal atypical teratoid rhabdoid tumor (AT/RT), shifting our understanding of embryonal tumor development. HML-2 expression is vital for proper human development and its expression is suppressed via methylation or chromatin remodeling as cells differentiate. We previously found that dysfunctional chromatin remodeling due to loss of SMARCB1 expression induces HML-2 envelope (env) expression, impairing cellular differentiation and migration, and facilitating tumor growth in AT/RT. Epigenetic dysregulation in other embryonal tumors with concomitant expression of stem-cell markers may facilitate HML-2 expression. Future studies could utilize HML-2 as potential diagnostic criteria, use its expression as a treatment biomarker, and investigate the efficacy of therapies targeting cells with high HML-2 expression.https://www.mdpi.com/2075-4426/11/12/1332endogenous retrovirusHERV-KHML-2developmental tumorsAT/RTbrain |
| spellingShingle | Tara T. Doucet-O’Hare Jared S. Rosenblum Ashish H. Shah Mark R. Gilbert Zhengping Zhuang Endogenous Retroviral Elements in Human Development and Central Nervous System Embryonal Tumors Journal of Personalized Medicine endogenous retrovirus HERV-K HML-2 developmental tumors AT/RT brain |
| title | Endogenous Retroviral Elements in Human Development and Central Nervous System Embryonal Tumors |
| title_full | Endogenous Retroviral Elements in Human Development and Central Nervous System Embryonal Tumors |
| title_fullStr | Endogenous Retroviral Elements in Human Development and Central Nervous System Embryonal Tumors |
| title_full_unstemmed | Endogenous Retroviral Elements in Human Development and Central Nervous System Embryonal Tumors |
| title_short | Endogenous Retroviral Elements in Human Development and Central Nervous System Embryonal Tumors |
| title_sort | endogenous retroviral elements in human development and central nervous system embryonal tumors |
| topic | endogenous retrovirus HERV-K HML-2 developmental tumors AT/RT brain |
| url | https://www.mdpi.com/2075-4426/11/12/1332 |
| work_keys_str_mv | AT taratdoucetohare endogenousretroviralelementsinhumandevelopmentandcentralnervoussystemembryonaltumors AT jaredsrosenblum endogenousretroviralelementsinhumandevelopmentandcentralnervoussystemembryonaltumors AT ashishhshah endogenousretroviralelementsinhumandevelopmentandcentralnervoussystemembryonaltumors AT markrgilbert endogenousretroviralelementsinhumandevelopmentandcentralnervoussystemembryonaltumors AT zhengpingzhuang endogenousretroviralelementsinhumandevelopmentandcentralnervoussystemembryonaltumors |