NGF/TRKA Decrease miR-145-5p Levels in Epithelial Ovarian Cancer Cells
Nerve Growth Factor (NGF) and its high-affinity receptor tropomyosin receptor kinase A (TRKA) increase their expression during the progression of epithelial ovarian cancer (EOC), promoting cell proliferation and angiogenesis through several oncogenic proteins, such as c-MYC and vascular endothelial...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/20/7657 |
| _version_ | 1797550785237614592 |
|---|---|
| author | Maritza P. Garrido Ignacio Torres Alba Avila Jonás Chnaiderman Manuel Valenzuela-Valderrama José Aramburo Lorena Oróstica Eduardo Durán-Jara Lorena Lobos-Gonzalez Carmen Romero |
| author_facet | Maritza P. Garrido Ignacio Torres Alba Avila Jonás Chnaiderman Manuel Valenzuela-Valderrama José Aramburo Lorena Oróstica Eduardo Durán-Jara Lorena Lobos-Gonzalez Carmen Romero |
| author_sort | Maritza P. Garrido |
| collection | DOAJ |
| description | Nerve Growth Factor (NGF) and its high-affinity receptor tropomyosin receptor kinase A (TRKA) increase their expression during the progression of epithelial ovarian cancer (EOC), promoting cell proliferation and angiogenesis through several oncogenic proteins, such as c-MYC and vascular endothelial growth factor (VEGF). The expression of these proteins is controlled by microRNAs (miRs), such as miR-145, whose dysregulation has been related to cancer. The aims of this work were to evaluate in EOC cells whether NGF/TRKA decreases miR-145 levels, and the effect of miR-145 upregulation. The levels of miR-145-5p were assessed by qPCR in ovarian biopsies and ovarian cell lines (human ovarian surface epithelial cells (HOSE), A2780 and SKOV3) stimulated with NGF. Overexpression of miR-145 in ovarian cells was used to evaluate cell proliferation, migration, invasion, c-MYC and VEGF protein levels, as well as tumor formation and metastasis in vivo. In EOC samples, miR-145-5p levels were lower than in epithelial ovarian tumors. Overexpression of miR-145 decreased cell proliferation, migration and invasion of EOC cells, changes that were concomitant with the decrease in c-MYC and VEGF protein levels. We observed decreased tumor formation and suppressed metastasis behavior in mice injected with EOC cells that overexpressed miR-145. As expected, ovarian cell lines stimulated with NGF diminished miR-145-5p transcription and abundance. These results suggest that the tumoral effects of NGF/TRKA depend on the regulation of miR-145-5p levels in EOC cells, and that its upregulation could be used as a possible therapeutic strategy for EOC. |
| first_indexed | 2024-03-10T15:34:21Z |
| format | Article |
| id | doaj.art-4947c31d9dec4b11b37eb7ea92e29cf3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:34:21Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4947c31d9dec4b11b37eb7ea92e29cf32023-11-20T17:20:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012120765710.3390/ijms21207657NGF/TRKA Decrease miR-145-5p Levels in Epithelial Ovarian Cancer CellsMaritza P. Garrido0Ignacio Torres1Alba Avila2Jonás Chnaiderman3Manuel Valenzuela-Valderrama4José Aramburo5Lorena Oróstica6Eduardo Durán-Jara7Lorena Lobos-Gonzalez8Carmen Romero9Laboratorio de Endocrinología y Biología de la Reproducción, Hospital Clínico Universidad de Chile, Santiago 8380456, ChileLaboratorio de Endocrinología y Biología de la Reproducción, Hospital Clínico Universidad de Chile, Santiago 8380456, ChileCentro de Medicina Regenerativa, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago 7710162, ChilePrograma de Virología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 8380453, ChileLaboratorio de Microbiología Celular. Instituto de Investigación e Innovación en Salud. Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago 8320000, ChileLaboratorio de Endocrinología y Biología de la Reproducción, Hospital Clínico Universidad de Chile, Santiago 8380456, ChileCentro de Investigación Biomédica (CIB), Facultad de Medicina, Universidad Diego Portales, Santiago 8370007, ChileCentro de Medicina Regenerativa, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago 7710162, ChileCentro de Medicina Regenerativa, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago 7710162, ChileLaboratorio de Endocrinología y Biología de la Reproducción, Hospital Clínico Universidad de Chile, Santiago 8380456, ChileNerve Growth Factor (NGF) and its high-affinity receptor tropomyosin receptor kinase A (TRKA) increase their expression during the progression of epithelial ovarian cancer (EOC), promoting cell proliferation and angiogenesis through several oncogenic proteins, such as c-MYC and vascular endothelial growth factor (VEGF). The expression of these proteins is controlled by microRNAs (miRs), such as miR-145, whose dysregulation has been related to cancer. The aims of this work were to evaluate in EOC cells whether NGF/TRKA decreases miR-145 levels, and the effect of miR-145 upregulation. The levels of miR-145-5p were assessed by qPCR in ovarian biopsies and ovarian cell lines (human ovarian surface epithelial cells (HOSE), A2780 and SKOV3) stimulated with NGF. Overexpression of miR-145 in ovarian cells was used to evaluate cell proliferation, migration, invasion, c-MYC and VEGF protein levels, as well as tumor formation and metastasis in vivo. In EOC samples, miR-145-5p levels were lower than in epithelial ovarian tumors. Overexpression of miR-145 decreased cell proliferation, migration and invasion of EOC cells, changes that were concomitant with the decrease in c-MYC and VEGF protein levels. We observed decreased tumor formation and suppressed metastasis behavior in mice injected with EOC cells that overexpressed miR-145. As expected, ovarian cell lines stimulated with NGF diminished miR-145-5p transcription and abundance. These results suggest that the tumoral effects of NGF/TRKA depend on the regulation of miR-145-5p levels in EOC cells, and that its upregulation could be used as a possible therapeutic strategy for EOC.https://www.mdpi.com/1422-0067/21/20/7657microRNA-145NGFTRKAepithelial ovarian cancerc-MYCVEGF |
| spellingShingle | Maritza P. Garrido Ignacio Torres Alba Avila Jonás Chnaiderman Manuel Valenzuela-Valderrama José Aramburo Lorena Oróstica Eduardo Durán-Jara Lorena Lobos-Gonzalez Carmen Romero NGF/TRKA Decrease miR-145-5p Levels in Epithelial Ovarian Cancer Cells International Journal of Molecular Sciences microRNA-145 NGF TRKA epithelial ovarian cancer c-MYC VEGF |
| title | NGF/TRKA Decrease miR-145-5p Levels in Epithelial Ovarian Cancer Cells |
| title_full | NGF/TRKA Decrease miR-145-5p Levels in Epithelial Ovarian Cancer Cells |
| title_fullStr | NGF/TRKA Decrease miR-145-5p Levels in Epithelial Ovarian Cancer Cells |
| title_full_unstemmed | NGF/TRKA Decrease miR-145-5p Levels in Epithelial Ovarian Cancer Cells |
| title_short | NGF/TRKA Decrease miR-145-5p Levels in Epithelial Ovarian Cancer Cells |
| title_sort | ngf trka decrease mir 145 5p levels in epithelial ovarian cancer cells |
| topic | microRNA-145 NGF TRKA epithelial ovarian cancer c-MYC VEGF |
| url | https://www.mdpi.com/1422-0067/21/20/7657 |
| work_keys_str_mv | AT maritzapgarrido ngftrkadecreasemir1455plevelsinepithelialovariancancercells AT ignaciotorres ngftrkadecreasemir1455plevelsinepithelialovariancancercells AT albaavila ngftrkadecreasemir1455plevelsinepithelialovariancancercells AT jonaschnaiderman ngftrkadecreasemir1455plevelsinepithelialovariancancercells AT manuelvalenzuelavalderrama ngftrkadecreasemir1455plevelsinepithelialovariancancercells AT josearamburo ngftrkadecreasemir1455plevelsinepithelialovariancancercells AT lorenaorostica ngftrkadecreasemir1455plevelsinepithelialovariancancercells AT eduardoduranjara ngftrkadecreasemir1455plevelsinepithelialovariancancercells AT lorenalobosgonzalez ngftrkadecreasemir1455plevelsinepithelialovariancancercells AT carmenromero ngftrkadecreasemir1455plevelsinepithelialovariancancercells |