Musashi-2 is a novel regulator of paclitaxel sensitivity in ovarian cancer cells.
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.
Research Institute for Molecular-Targeted Drugs, Department of Biological Engineering, Konkuk University, Seoul 05029, Republic of Korea.
Jeongsuk
J
Lee
Research Institute for Molecular-Targeted Drugs, Department of Biological Engineering, Konkuk University, Seoul 05029, Republic of Korea.
Sungkwan
S
An
Research Institute for Molecular-Targeted Drugs, Department of Biological Engineering, Konkuk University, Seoul 05029, Republic of Korea.
Yeong Min
YM
Choi
Research Institute for Molecular-Targeted Drugs, Department of Biological Engineering, Konkuk University, Seoul 05029, Republic of Korea.
Junwoo
J
Lee
Department of Dermatology, Konkuk University School of Medicine, Seoul 05030, Republic of Korea.
Kyu Joong
KJ
Ahn
Laboratory of Molecular Oncology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul 04619, Republic of Korea.
Jae Ho
JH
Lee
Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul 04619, Republic of Korea.
Tae Jin
TJ
Kim
Gene Cell Pharm Corporation, Cheongju-si, Chungcheongbuk-do 28160, Republic of Korea.
In-Sook
IS
An
Research Institute for Molecular-Targeted Drugs, Department of Biological Engineering, Konkuk University, Seoul 05029, Republic of Korea.
Seunghee
S
Bae
D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; C438151:MSI2 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D017239:Paclitaxel