RBM3-regulated genes promote DNA integrity and affect clinical outcome in epithelial ovarian cancer
2011 (English)In: Translational Oncology, ISSN 1936-5233, Vol. 4, no 4, 202-211 p.Article in journal (Refereed) Published
The RNA-binding motif protein 3 (RBM3) was initially discovered as a putative cancer biomarker based on its differential expression in various cancer forms in the Human Protein Atlas (HPA). We previously reported an association between high expression of RBM3 and prolonged survival in breast and epithelial ovarian cancer (EOC). Because the function of RBM3 has not been fully elucidated, the aim of this study was to use gene set enrichment analysis to identify the underlying biologic processes associated with RBM3 expression in a previously analyzed EOC cohort (cohort 1, n = 267). This revealed an association between RBM3 expression and several cellular processes involved in the maintenance of DNA integrity. RBM3-regulated genes were subsequently screened in the HPA to select for putative prognostic markers, and candidate proteins were analyzed in the ovarian cancer cell line A2780, whereby an up-regulation of Chk1, Chk2, and MCM3 was demonstrated in siRBM3-treated cells compared to controls. The prognostic value of these markers was assessed at the messenger RNA level in cohort 1 and the protein level in an independent EOC cohort (cohort 2, n = 154). High expression levels of Chk1, Chk2, and MCM3 were associated with a significantly shorter survival in both cohorts, and phosphorylated Chk2 was an adverse prognostic marker in cohort 2. These results uncover a putative role for RBM3 in DNA damage response, which might, in part, explain its cisplatin-sensitizing properties and good prognostic value in EOC. Furthermore, it is demonstrated that Chk1, Chk2, and MCM3 are poor prognostic markers in EOC.
Place, publisher, year, edition, pages
2011. Vol. 4, no 4, 202-211 p.
checkpoint kinase 1, checkpoint kinase 2, cisplatin, DNA, messenger RNA, minichromosome maintenance protein 3, RNA binding motif protein 3, RNA binding protein, unclassified drug, article, cancer cell, DNA damage, epithelial ovarian cancer, genetic analysis, human, human cell, in vitro study, ovary cancer, prognosis, protein blood level, protein expression, protein phosphorylation, tissue microarray
Cancer and Oncology
IdentifiersURN: urn:nbn:se:kth:diva-151168DOI: 10.1593/tlo.11106PubMedID: 21804916ScopusID: 2-s2.0-79960336702OAI: oai:DiVA.org:kth-151168DiVA: diva2:747649
QC 201409172014-09-172014-09-152015-10-09Bibliographically approved