Jing Li, Gong Mi, Lu Xiaoyuan, Jiang Yi, Li Huijian, Cheng Wenjun
Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University Nanjing, People's Republic of China.
Department of Gynecology, The Affiliated Hospital of Xuzhou Medical University Xuzhou, People's Republic of China.
Am J Transl Res. 2019 Jan 15;11(1):406-417. eCollection 2019.
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.
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.
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.
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.
卵巢癌具有高死亡率和预后差的特点。然而，卵巢癌的发病机制仍不清楚。在我们的研究中，我们聚焦于长链非编码RNA LINC01127在卵巢癌发病机制中的潜在作用及其潜在机制。
通过生物信息学分析筛选出可能参与卵巢癌发展的LINC01127。采用基因集富集分析（GSEA）来分析LINC01127的功能。运用实时定量聚合酶链反应（QRT-PCR）分析72例卵巢癌组织和53例正常卵巢组织中LINC01127的水平。同时也通过qRT-PCR测定卵巢癌细胞系中LINC01127的水平。随后，使用Lipofectamine 2000将LINC01127小干扰RNA转染至所选的卵巢肿瘤细胞，接着采用流式细胞术检测细胞周期。通过肿瘤形成实验验证LINC01127对裸鼠肿瘤生长和细胞周期的调节作用。通过蛋白质免疫印迹法进一步探究LINC01127参与细胞周期调控的机制。
卵巢癌组织中LINC01127的表达显著高于正常卵巢组织。LINC01127的表达水平与卵巢癌患者的预后呈负相关。GSEA分析表明，LINC01127主要富集于细胞周期调控。转染LINC01127小干扰RNA后，SKOV3和HO8910细胞的增殖能力受到抑制，细胞周期停滞在G1/G0期。裸鼠致瘤性实验表明，LINC01127低表达抑制卵巢肿瘤生长。进一步研究发现，敲低LINC01127可上调细胞周期蛋白D、细胞周期蛋白E和细胞周期蛋白依赖性激酶4的表达水平，但显著上调P16和P21的表达水平。同时，敲低LINC01127可抑制AKT和ERK信号通路。
LINC01127在卵巢癌组织中上调。LINC01127可能通过促进ERK和AKT磷酸化加速细胞周期进程，从而参与卵巢癌的发展。
