Lee Jeongsuk, An Sungkwan, Choi Yeong Min, Lee Junwoo, Ahn Kyu Joong, Lee Jae Ho, Kim Tae Jin, An In-Sook, Bae Seunghee
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.
Int J Oncol. 2016 Nov;49(5):1945-1952. doi: 10.3892/ijo.2016.3683. Epub 2016 Sep 6.
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.
由于已确定的预后标志物和症状较少，卵巢癌通常在晚期才被诊断出来，并且大多数患者会复发并对紫杉醇等抗癌药物产生耐药性。Musashi-2（MSI2）是一种基因翻译调节因子，作为一种致癌蛋白，是各类癌症预后不良的标志物。然而，MSI2在卵巢癌中的生物学和临床意义仍不清楚。我们使用基于组织微阵列的检测方法，证明MSI2在晚期浆液性卵巢癌组织中高表达。此外，过表达MSI2的卵巢癌细胞表现出活力、增殖和生长能力增强。我们发现MSI2在耐紫杉醇的卵巢癌SKOV3-TR细胞中过表达，但在紫杉醇敏感细胞系中未过表达。使用细胞活力和凋亡检测方法确定，慢病毒介导的稳定敲低MSI2的SKOV3-TR细胞中MSI2表达缺失会损害紫杉醇耐药性。相反，慢病毒介导的MSI2过表达促进了紫杉醇敏感的卵巢癌细胞中紫杉醇耐药性的发展。本研究结果首次证明，MSI2是晚期浆液性卵巢癌的一个有价值的标志物，并且MSI2在紫杉醇耐药中起重要作用。
