Abstract
BackgroundStudies of alternative mRNA splicing (AS) in health and disease have yet to yield the complete picture of protein diversity and its role in physiology and pathology. Some forms of cancer appear to be associated to certain alternative mRNA splice variants, but their role in the cancer development and outcome is unclear.MethodsWe examined AS profiles by means of whole genome exon expression microarrays (Affymetrix GeneChip 1.0) in ovarian tumors and ovarian cancer-derived cell lines, compared to healthy ovarian tissue. Alternatively spliced genes expressed predominantly in ovarian tumors and cell lines were confirmed by RT-PCR.ResultsAmong several significantly overexpressed AS genes in malignant ovarian tumors and ovarian cancer cell lines, the most significant one was that of the zinc finger protein ZNF695, with two previously unknown mRNA splice variants identified in ovarian tumors and cell lines. The identity of ZNF695 AS variants was confirmed by cloning and sequencing of the amplicons obtained from ovarian cancer tissue and cell lines.ConclusionsAlternative ZNF695 mRNA splicing could be a marker of ovarian cancer with possible implications on its pathogenesis.
Highlights
Studies of alternative mRNA splicing (AS) in health and disease have yet to yield the complete picture of protein diversity and its role in physiology and pathology
After informed consent was obtained, normal ovarian tissue (HOT), borderline ovarian tumor (BOT), malignant epithelial ovarian tumors stages III and IV (MOT) tissues were collected by the clinical partners at the Oncology Hospital, National Medical Center Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), and at the General Hospital of Mexico SSA (Secretaría de Salud) from patients with diagnosed ovarian cancer, or healthy ovarian tissue from patients who underwent abdominal surgery for hysterectomy due to uterine myomatosis with no evidence of ovarian pathology
Expression microarray assays A total of 14 samples with an RNA integrity number (RIN) ≥ 8 were hybridized in GeneChip 1.0 microarrays according to the MIAME guidelines
Summary
Studies of alternative mRNA splicing (AS) in health and disease have yet to yield the complete picture of protein diversity and its role in physiology and pathology. Some forms of cancer appear to be associated to certain alternative mRNA splice variants, but their role in the cancer development and outcome is unclear. Alternative splicing (AS) provides a critical and flexible layer of regulation, intervening in many biological processes, such as the diversity of proteins. AS could play an important role in gene regulation both in health and disease. AS could affect the cellular processes related to tumor progression, including inhibition of apoptosis, tumor invasiveness, metastasis and angiogenesis [14]
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