Li Jing1,2, Mi Gong1, Xiaoyuan Lu2, Yi Jiang1, Huijian Li1,3,4,5, Wenjun Cheng1. 1. Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University Nanjing, People's Republic of China. 2. Department of Gynecology, The Affiliated Hospital of Xuzhou Medical University Xuzhou, People's Republic of China. 3. State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University Nanjing, People's Republic of China. 4. Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University Nanjing, People's Republic of China. 5. Department of Gynecology, Wuxi Maternal and Child Health Hospital Wuxi, People's Republic of China.
Abstract
BACKGROUND: Ovarian cancer is characterized by the high mortality rate and poor prognosis. Nevertheless, the oncogenesis mechanisms of ovarian cancer remain unclear. In our study, we focused on the potential role of lncRNA LINC01127 in the pathogenesis of ovarian cancer and its underlying mechanism. METHODS: LINC01127, which may participate in the development of ovarian cancer, was screened out by bioinformatics analysis. GSEA was used to analyze the function of LINC01127. QRT-PCR was used to analyze the LINC01127 level in 72 cases of ovarian cancer tissues and 53 cases of normal ovarian tissues. LINC01127 level in ovarian cancer cell lines was also determined by qRT-PCR. Subsequently, the selected ovarian tumor cells were transfected with LINC01127 siRNA by Lipofectamine 2000, followed by cell cycle detection using flow cytometry. The regulatory effects of LINC01127 on tumor growth and cell cycle in nude mice were verified by tumor formation assay. The mechanism of LINC01127 involving in cell cycle regulation was further explored by Western Blot. RESULTS: LINC01127 expression in ovarian cancer tissues was significantly higher than that in normal ovary tissues. The expression level of LINC01127 was negatively correlated with the prognosis of patients with ovarian cancer. GSEA analysis showed that LINC01127 was mainly enriched in the regulation of cell cycle. After transfection with LINC01127 siRNA, the proliferative abilities of SKOV3 and HO8910 cells were inhibited and cell cycle was arrested at G1/G0 phase. Tumorigenicity assay in nude mice showed that low expression of LINC01127 inhibited the growth of ovarian tumors. Further study found that LINC01127 knockdown upregulated expression levels of Cyclin D, Cyclin E and CDK4, but dramatically upregulated expression levels of P16 and P21. Meanwhile, the AKT and ERK pathways were inhibited by LINC01127 knockdown. CONCLUSIONS: LINC01127 was up-regulated in ovarian cancer tissues. LINC01127 may be involved in the development of ovarian cancer by accelerating cell cycle progression through promoting the phosphorylation of ERK and AKT.
BACKGROUND:Ovarian cancer is characterized by the high mortality rate and poor prognosis. Nevertheless, the oncogenesis mechanisms of ovarian cancer remain unclear. In our study, we focused on the potential role of lncRNA LINC01127 in the pathogenesis of ovarian cancer and its underlying mechanism. METHODS:LINC01127, which may participate in the development of ovarian cancer, was screened out by bioinformatics analysis. GSEA was used to analyze the function of LINC01127. QRT-PCR was used to analyze the LINC01127 level in 72 cases of ovarian cancer tissues and 53 cases of normal ovarian tissues. LINC01127 level in ovarian cancer cell lines was also determined by qRT-PCR. Subsequently, the selected ovarian tumor cells were transfected with LINC01127 siRNA by Lipofectamine 2000, followed by cell cycle detection using flow cytometry. The regulatory effects of LINC01127 on tumor growth and cell cycle in nude mice were verified by tumor formation assay. The mechanism of LINC01127 involving in cell cycle regulation was further explored by Western Blot. RESULTS:LINC01127 expression in ovarian cancer tissues was significantly higher than that in normal ovary tissues. The expression level of LINC01127 was negatively correlated with the prognosis of patients with ovarian cancer. GSEA analysis showed that LINC01127 was mainly enriched in the regulation of cell cycle. After transfection with LINC01127 siRNA, the proliferative abilities of SKOV3 and HO8910 cells were inhibited and cell cycle was arrested at G1/G0 phase. Tumorigenicity assay in nude mice showed that low expression of LINC01127 inhibited the growth of ovarian tumors. Further study found that LINC01127 knockdown upregulated expression levels of Cyclin D, Cyclin E and CDK4, but dramatically upregulated expression levels of P16 and P21. Meanwhile, the AKT and ERK pathways were inhibited by LINC01127 knockdown. CONCLUSIONS:LINC01127 was up-regulated in ovarian cancer tissues. LINC01127 may be involved in the development of ovarian cancer by accelerating cell cycle progression through promoting the phosphorylation of ERK and AKT.