Abstract
As few prognostic markers and symptoms have been identified, ovarian cancer is typically diagnosed at an advanced stage, and a majority of patients will relapse and develop resistance to anticancer drugs such as paclitaxel. Musashi-2 (MSI2) is a regulator of gene translation and functions as an oncogenic protein and a marker of poor prognosis in various types of cancer. However, the biological and clinical significance of MSI2 in ovarian cancer remains unclear. Using a tissue microarray-based assay, we demonstrated that MSI2 was highly expressed in advanced, serous ovarian cancer tissues. In addition, MSI2-overexpressing ovarian cancer cells exhibited increased viability, proliferation and growth. We found that MSI2 was overexpressed in paclitaxel-resistant ovarian cancer SKOV3-TR cells but not in paclitaxel-sensitive cell lines. The loss of MSI2 expression in lentivirus-mediated stable MSI2 knockdown SKOV3-TR cells impaired paclitaxel resistance as determined using cell viability and apoptosis assays. In contrast, lentivirus-mediated MSI2 overexpression promoted the development of paclitaxel resistance in paclitaxel-sensitive ovarian cancer cells. The results of the present study are the first to demonstrate that MSI2 is a valuable marker of advanced, serous ovarian cancer and that MSI2 plays an important role in paclitaxel resistance.
MeSH terms
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Adenocarcinoma, Clear Cell / drug therapy
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Adenocarcinoma, Clear Cell / metabolism
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Adenocarcinoma, Clear Cell / pathology
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Adenocarcinoma, Mucinous / drug therapy
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Adenocarcinoma, Mucinous / metabolism
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Adenocarcinoma, Mucinous / pathology
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Antineoplastic Agents, Phytogenic / pharmacology
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Apoptosis
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism*
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Blotting, Western
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Cell Proliferation
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Cystadenocarcinoma, Serous / drug therapy
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Cystadenocarcinoma, Serous / metabolism
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Cystadenocarcinoma, Serous / pathology
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Drug Resistance, Neoplasm*
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Endometrial Neoplasms / drug therapy
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Endometrial Neoplasms / metabolism
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Endometrial Neoplasms / pathology
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Female
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Gene Expression Regulation, Neoplastic / drug effects*
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Humans
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Immunoenzyme Techniques
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Neoplasm Recurrence, Local / drug therapy
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Neoplasm Recurrence, Local / metabolism
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Neoplasm Recurrence, Local / pathology*
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Neoplasm Staging
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Ovarian Neoplasms / drug therapy
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Ovarian Neoplasms / metabolism
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Ovarian Neoplasms / pathology*
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Paclitaxel / pharmacology*
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Prognosis
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RNA, Messenger / genetics
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism*
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents, Phytogenic
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Biomarkers, Tumor
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MSI2 protein, human
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RNA, Messenger
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RNA-Binding Proteins
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Paclitaxel