Musashi-2 is a novel regulator of paclitaxel sensitivity in ovarian cancer cells

Lee,Jeongsuk; An,Sungkwan; Choi,Yeong Min; Lee,Junwoo; Ahn,Kyu Joong; Lee,Jae Ho; Kim,Tae Jin; An,In-Sook; Bae,Seunghee

doi:10.3892/ijo.2016.3683

Musashi-2 is a novel regulator of paclitaxel sensitivity in ovarian cancer cells

Authors:
- Jeongsuk Lee
- Sungkwan An
- Yeong Min Choi
- Junwoo Lee
- Kyu Joong Ahn
- Jae Ho Lee
- Tae Jin Kim
- In-Sook An
- Seunghee Bae
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Affiliations: Research Institute for Molecular-Targeted Drugs, Department of Biological Engineering, Konkuk University, Seoul 05029, Republic of Korea, Department of Dermatology, Konkuk University School of Medicine, Seoul 05030, Republic of Korea, Laboratory of Molecular Oncology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul 04619, Republic of Korea, Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul 04619, Republic of Korea, Gene Cell Pharm Corporation, Cheongju-si, Chungcheongbuk-do 28160, Republic of Korea
Published online on: September 6, 2016 https://doi.org/10.3892/ijo.2016.3683
Pages: 1945-1952

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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.

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