The HMGB1-2 Ovarian Cancer Interactome. The Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-Response.
chemotherapy
interactome
ovarian cancer
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
27 Aug 2020
27 Aug 2020
Historique:
received:
09
07
2020
revised:
22
08
2020
accepted:
24
08
2020
entrez:
2
9
2020
pubmed:
2
9
2020
medline:
2
9
2020
Statut:
epublish
Résumé
High mobility group box B (HMGB) proteins are overexpressed in different types of cancers such as epithelial ovarian cancers (EOC). We have determined the first interactome of HMGB1 and HMGB2 in epithelial ovarian cancer (the EOC-HMGB interactome). Libraries from the SKOV-3 cell line and a primary transitional cell carcinoma (TCC) ovarian tumor were tested by the Yeast Two Hybrid (Y2H) approach. The interactome reveals proteins that are related to cancer hallmarks and their expression is altered in EOC. Moreover, some of these proteins have been associated to survival and prognosis of patients. The interaction of MIEN1 and NOP53 with HMGB2 has been validated by co-immunoprecipitation in SKOV-3 and PEO1 cell lines. SKOV-3 cells were treated with different anti-tumoral drugs to evaluate changes in HMGB1, HMGB2, MIEN1 and NOP53 gene expression. Results show that combined treatment of paclitaxel and carboplatin induces a stronger down-regulation of these genes in comparison to individual treatments. Individual treatment with paclitaxel or olaparib up-regulates NOP53, which is expressed at lower levels in EOC than in non-cancerous cells. On the other hand, bevacizumab diminishes the expression of HMGB2 and NOP53. This study also shows that silencing of these genes affects cell-viability after drug exposure. HMGB1 silencing causes loss of response to paclitaxel, whereas silencing of HMGB2 slightly increases sensitivity to olaparib. Silencing of either HMGB1 or HMGB2 increases sensitivity to carboplatin. Lastly, a moderate loss of response to bevacizumab is observed when NOP53 is silenced.
Identifiants
pubmed: 32867128
pii: cancers12092435
doi: 10.3390/cancers12092435
pmc: PMC7564582
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Instituto de Salud Carlos III
ID : PI14/01031
Organisme : Instituto de Salud Carlos III
ID : PI18/01714
Organisme : Xunta de Galicia
ID : ED431C 2016-012
Organisme : European Regional Development Fund
ID : PI14/01031 PI18/01714
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