Lycorine weakens tamoxifen resistance of breast cancer via abrogating HAGLR‐mediated epigenetic suppression on VGLL4 by DNMT1
Abstract Much is known about the significance of lycorine, a natural alkaloid, in combating various types of cancer, including breast cancer (BC), but whether it participates in regulating tamoxifen (TAM) resistance and its underlying mechanism remain to be elucidated. Tamoxifen‐resistant (TAMR) BC...
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| Format: | Article |
| Language: | English |
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Wiley
2023-03-01
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| Series: | Kaohsiung Journal of Medical Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/kjm2.12636 |
| _version_ | 1811157630717001728 |
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| author | Jing Zhai Jun‐Feng Jiang Lei Shi |
| author_facet | Jing Zhai Jun‐Feng Jiang Lei Shi |
| author_sort | Jing Zhai |
| collection | DOAJ |
| description | Abstract Much is known about the significance of lycorine, a natural alkaloid, in combating various types of cancer, including breast cancer (BC), but whether it participates in regulating tamoxifen (TAM) resistance and its underlying mechanism remain to be elucidated. Tamoxifen‐resistant (TAMR) BC cells were first established by continuously exposed to increasing concentrations of TAM. Levels of targeted gene including HOXD antisense growth‐associated lncRNA (HAGLR) and Vestigial like family member 4 (VGLL4) were analyzed by qRT‐PCR and western blot, respectively. Cell proliferation ability was assessed by MTT and EdU assays. Flow cytometry was carried out to evaluate the apoptosis. VGLL4 promoter methylation was examined using methylation specific PCR (MSP). The role of HAGLR acting on the expression of VGLL4 via DNA hypermethylation was confirmed by RNA immunoprecipitation (RIP). Here, we reported that lycorine administration reduced the survival ratio of TAMR BC cells, decreased the IC50 of TAM, and strengthened TAM‐induced apoptosis. HAGLR, observed to be highly expressed in TAMR BC cells, was identified to be a downstream effector of lycorine, of which overexpression abolished lycorine‐mediated TAMR inhibition. VGLL4 served as a target of HAGLR in regulating lycorine‐mediated suppression on tamoxifen resistance of TAMR BC cells. Mechanistically, HAGLR epigenetically suppressed VGLL4 expression via DNA methyltransferase 1 (DNMT1)‐mediated DNA hypermethylation. Taken together, our data highlights the pivotal role of lycorine in TAM resistance of BC, which may provide a potential agent for improving the effectiveness and efficacy of BC resistance. |
| first_indexed | 2024-04-10T05:09:23Z |
| format | Article |
| id | doaj.art-6392e914eaa746f1affc4d67a5a137a3 |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-04-10T05:09:23Z |
| publishDate | 2023-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-6392e914eaa746f1affc4d67a5a137a32023-03-09T09:24:20ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502023-03-0139327828910.1002/kjm2.12636Lycorine weakens tamoxifen resistance of breast cancer via abrogating HAGLR‐mediated epigenetic suppression on VGLL4 by DNMT1Jing Zhai0Jun‐Feng Jiang1Lei Shi2Department of Pharmacy Gansu provincial Hospital Lanzhou Gansu Province People's Republic of ChinaDivision of Oncology Gansu Provincial Cancer Hospital Lanzhou Gansu Province People's Republic of ChinaDepartment of Pharmacy Gansu provincial Hospital Lanzhou Gansu Province People's Republic of ChinaAbstract Much is known about the significance of lycorine, a natural alkaloid, in combating various types of cancer, including breast cancer (BC), but whether it participates in regulating tamoxifen (TAM) resistance and its underlying mechanism remain to be elucidated. Tamoxifen‐resistant (TAMR) BC cells were first established by continuously exposed to increasing concentrations of TAM. Levels of targeted gene including HOXD antisense growth‐associated lncRNA (HAGLR) and Vestigial like family member 4 (VGLL4) were analyzed by qRT‐PCR and western blot, respectively. Cell proliferation ability was assessed by MTT and EdU assays. Flow cytometry was carried out to evaluate the apoptosis. VGLL4 promoter methylation was examined using methylation specific PCR (MSP). The role of HAGLR acting on the expression of VGLL4 via DNA hypermethylation was confirmed by RNA immunoprecipitation (RIP). Here, we reported that lycorine administration reduced the survival ratio of TAMR BC cells, decreased the IC50 of TAM, and strengthened TAM‐induced apoptosis. HAGLR, observed to be highly expressed in TAMR BC cells, was identified to be a downstream effector of lycorine, of which overexpression abolished lycorine‐mediated TAMR inhibition. VGLL4 served as a target of HAGLR in regulating lycorine‐mediated suppression on tamoxifen resistance of TAMR BC cells. Mechanistically, HAGLR epigenetically suppressed VGLL4 expression via DNA methyltransferase 1 (DNMT1)‐mediated DNA hypermethylation. Taken together, our data highlights the pivotal role of lycorine in TAM resistance of BC, which may provide a potential agent for improving the effectiveness and efficacy of BC resistance.https://doi.org/10.1002/kjm2.12636DNA hypermethylationHAGLRlycorinetamoxifen resistanceVGLL4 |
| spellingShingle | Jing Zhai Jun‐Feng Jiang Lei Shi Lycorine weakens tamoxifen resistance of breast cancer via abrogating HAGLR‐mediated epigenetic suppression on VGLL4 by DNMT1 Kaohsiung Journal of Medical Sciences DNA hypermethylation HAGLR lycorine tamoxifen resistance VGLL4 |
| title | Lycorine weakens tamoxifen resistance of breast cancer via abrogating HAGLR‐mediated epigenetic suppression on VGLL4 by DNMT1 |
| title_full | Lycorine weakens tamoxifen resistance of breast cancer via abrogating HAGLR‐mediated epigenetic suppression on VGLL4 by DNMT1 |
| title_fullStr | Lycorine weakens tamoxifen resistance of breast cancer via abrogating HAGLR‐mediated epigenetic suppression on VGLL4 by DNMT1 |
| title_full_unstemmed | Lycorine weakens tamoxifen resistance of breast cancer via abrogating HAGLR‐mediated epigenetic suppression on VGLL4 by DNMT1 |
| title_short | Lycorine weakens tamoxifen resistance of breast cancer via abrogating HAGLR‐mediated epigenetic suppression on VGLL4 by DNMT1 |
| title_sort | lycorine weakens tamoxifen resistance of breast cancer via abrogating haglr mediated epigenetic suppression on vgll4 by dnmt1 |
| topic | DNA hypermethylation HAGLR lycorine tamoxifen resistance VGLL4 |
| url | https://doi.org/10.1002/kjm2.12636 |
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