Cargando…
LncRNA ANRIL affects the sensitivity of ovarian cancer to cisplatin via regulation of let-7a/HMGA2 axis
This paper tried to explore ANRIL expression in ovarian cancer and how it affects cisplatin-sensitivity of ovarian cancer cells via regulation of let-7a/high-mobility group protein A2 (HMGA2) axis. qRT-PCR was used to detect ANRIL and let-7a levels in ovarian cancer tissues and cell lines (SKOV3 and...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609561/ https://www.ncbi.nlm.nih.gov/pubmed/31189742 http://dx.doi.org/10.1042/BSR20182101 |
_version_ | 1783432332097617920 |
---|---|
author | Miao, Jin-Tian Gao, Jian-Hua Chen, Yong-Qian Chen, Hong Meng, Hao-Yi Lou, Ge |
author_facet | Miao, Jin-Tian Gao, Jian-Hua Chen, Yong-Qian Chen, Hong Meng, Hao-Yi Lou, Ge |
author_sort | Miao, Jin-Tian |
collection | PubMed |
description | This paper tried to explore ANRIL expression in ovarian cancer and how it affects cisplatin-sensitivity of ovarian cancer cells via regulation of let-7a/high-mobility group protein A2 (HMGA2) axis. qRT-PCR was used to detect ANRIL and let-7a levels in ovarian cancer tissues and cell lines (SKOV3 and SKOV3/DDP). Then cells were randomly assigned into Blank, negative control siRNA, ANRIL siRNA, let-7a inhibitor, and ANRIL siRNA+let-7a-inhibitor groups. CCK-8 assay was applied for assessing cell viability of cells treated with different concentrations of cisplatin. Flow cytometry was employed to test cell apoptosis rate. qRT-PCR and Western blot were performed for related molecules detection. Nude mice transplanted with SKOV3/DDP cells were used to confirm the effects of ANRIL siRNA on the cisplatin-sensitivity. Ovarian cancer tissues and cisplatin-resistant cells had increased ANRIL expression and decreased let-7a expression, and those patients with higher clinical stage and pathological grade showed higher ANRIL and lower let-7a. Dual-luciferase reporter-gene assay confirmed the targeting relationship between ANRIL and let-7a, and between let-7a and HMGA2. The cell viability and cisplatin IC(50) were decreased in ANRIL siRNA group exposed to different concentrations of cisplatin, with enhanced apoptosis, as well as elevated let-7a and declined HMGA2, which would be reversed by let-7a inhibitor. Meanwhile, ANRIL down-regulation enhanced the inhibitory effect of cisplatin on tumor growth of nude mice and reduced tumor weight. Silencing ANRIL expression reduced HMGA2 expression to promote the apoptosis and improve cisplatin-sensitivity of ovarian cancer cells via up-regulating let-7a expression. |
format | Online Article Text |
id | pubmed-6609561 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66095612019-07-11 LncRNA ANRIL affects the sensitivity of ovarian cancer to cisplatin via regulation of let-7a/HMGA2 axis Miao, Jin-Tian Gao, Jian-Hua Chen, Yong-Qian Chen, Hong Meng, Hao-Yi Lou, Ge Biosci Rep Research Articles This paper tried to explore ANRIL expression in ovarian cancer and how it affects cisplatin-sensitivity of ovarian cancer cells via regulation of let-7a/high-mobility group protein A2 (HMGA2) axis. qRT-PCR was used to detect ANRIL and let-7a levels in ovarian cancer tissues and cell lines (SKOV3 and SKOV3/DDP). Then cells were randomly assigned into Blank, negative control siRNA, ANRIL siRNA, let-7a inhibitor, and ANRIL siRNA+let-7a-inhibitor groups. CCK-8 assay was applied for assessing cell viability of cells treated with different concentrations of cisplatin. Flow cytometry was employed to test cell apoptosis rate. qRT-PCR and Western blot were performed for related molecules detection. Nude mice transplanted with SKOV3/DDP cells were used to confirm the effects of ANRIL siRNA on the cisplatin-sensitivity. Ovarian cancer tissues and cisplatin-resistant cells had increased ANRIL expression and decreased let-7a expression, and those patients with higher clinical stage and pathological grade showed higher ANRIL and lower let-7a. Dual-luciferase reporter-gene assay confirmed the targeting relationship between ANRIL and let-7a, and between let-7a and HMGA2. The cell viability and cisplatin IC(50) were decreased in ANRIL siRNA group exposed to different concentrations of cisplatin, with enhanced apoptosis, as well as elevated let-7a and declined HMGA2, which would be reversed by let-7a inhibitor. Meanwhile, ANRIL down-regulation enhanced the inhibitory effect of cisplatin on tumor growth of nude mice and reduced tumor weight. Silencing ANRIL expression reduced HMGA2 expression to promote the apoptosis and improve cisplatin-sensitivity of ovarian cancer cells via up-regulating let-7a expression. Portland Press Ltd. 2019-07-05 /pmc/articles/PMC6609561/ /pubmed/31189742 http://dx.doi.org/10.1042/BSR20182101 Text en © 2019 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Articles Miao, Jin-Tian Gao, Jian-Hua Chen, Yong-Qian Chen, Hong Meng, Hao-Yi Lou, Ge LncRNA ANRIL affects the sensitivity of ovarian cancer to cisplatin via regulation of let-7a/HMGA2 axis |
title | LncRNA ANRIL affects the sensitivity of ovarian cancer to cisplatin via regulation of let-7a/HMGA2 axis |
title_full | LncRNA ANRIL affects the sensitivity of ovarian cancer to cisplatin via regulation of let-7a/HMGA2 axis |
title_fullStr | LncRNA ANRIL affects the sensitivity of ovarian cancer to cisplatin via regulation of let-7a/HMGA2 axis |
title_full_unstemmed | LncRNA ANRIL affects the sensitivity of ovarian cancer to cisplatin via regulation of let-7a/HMGA2 axis |
title_short | LncRNA ANRIL affects the sensitivity of ovarian cancer to cisplatin via regulation of let-7a/HMGA2 axis |
title_sort | lncrna anril affects the sensitivity of ovarian cancer to cisplatin via regulation of let-7a/hmga2 axis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609561/ https://www.ncbi.nlm.nih.gov/pubmed/31189742 http://dx.doi.org/10.1042/BSR20182101 |
work_keys_str_mv | AT miaojintian lncrnaanrilaffectsthesensitivityofovariancancertocisplatinviaregulationoflet7ahmga2axis AT gaojianhua lncrnaanrilaffectsthesensitivityofovariancancertocisplatinviaregulationoflet7ahmga2axis AT chenyongqian lncrnaanrilaffectsthesensitivityofovariancancertocisplatinviaregulationoflet7ahmga2axis AT chenhong lncrnaanrilaffectsthesensitivityofovariancancertocisplatinviaregulationoflet7ahmga2axis AT menghaoyi lncrnaanrilaffectsthesensitivityofovariancancertocisplatinviaregulationoflet7ahmga2axis AT louge lncrnaanrilaffectsthesensitivityofovariancancertocisplatinviaregulationoflet7ahmga2axis |