Yim Ga Won, Kim Hee Jung, Kim Lee Kyung, Kim Sang Wun, Kim Sunghoon, Nam Eun Ji, Kim Young Tae
Department of Obstetrics and Gynecology, National Medical Center, Seoul, Korea.
Department of Obstetrics and Gynecology, Yonsei University Graduate School, Seoul, Korea.
Cancer Res Treat. 2017 Jul;49(3):656-668. doi: 10.4143/crt.2016.263. Epub 2016 Oct 11.
The biological function of long non-coding RNAs (lncRNAs) is only partially understood; therefore, in this study, we investigated the expression of the novel antisense () lncRNA and its oncogenic role in serous ovarian cancer (SOC).
expression was examined in 129 SOC tissue samples by real time reverse transcription polymerase chain reaction. Clinicopathological factors and patient survival were compared between the high (n=27) and low expression group (n=102). To investigate the role of in cell proliferation, invasion, and migration, expression in ovarian cancer cells was knocked down using RNA interference.
expression in cancer tissue was 77-fold higher than that of noncancerous tissue (p < 0.05). Higher expression was significantly correlated with histological grade (p=0.017) and preoperative cancer antigen 125 (p=0.048). overexpression in SOC cells led to increased cell proliferation, invasion, and migration. Moreover, was associated with the expression of genes involved in cell invasion, migration, and epithelial-mesenchymal transition (EMT), including vascular endothelial growth factor, matrix metalloproteinase 9 (MMP-9), B-catenin, E-cadherin, Snail, Twist, and vimentin. Multivariate analysis revealed that was a prognostic factor of progressive disease and mortality (hazard ratio [HR], 1.730; p=0.043 and HR, 2.170; p=0.033, respectively). Progression-free and overall survival were significantly shorter in patients with high expression.
These findings highlight the clinical significance of to predicting the prognosis of SOC patients and suggest its potential in promoting tumor aggressiveness via regulation of vascular endothelial growth factor (VEGF), MMP-9, and EMT-related mechanisms.
长链非编码RNA(lncRNAs)的生物学功能仅得到部分了解;因此,在本研究中,我们调查了新型反义lncRNA的表达及其在浆液性卵巢癌(SOC)中的致癌作用。
通过实时逆转录聚合酶链反应检测129例SOC组织样本中的lncRNA表达。比较高表达组(n = 27)和低表达组(n = 102)之间的临床病理因素和患者生存率。为了研究lncRNA在细胞增殖、侵袭和迁移中的作用,使用RNA干扰敲低卵巢癌细胞中的lncRNA表达。
癌组织中的lncRNA表达比非癌组织高77倍(p < 0.05)。较高的lncRNA表达与组织学分级(p = 0.017)和术前癌抗原125(p = 0.048)显著相关。SOC细胞中lncRNA的过表达导致细胞增殖、侵袭和迁移增加。此外,lncRNA与参与细胞侵袭、迁移和上皮-间质转化(EMT)的基因表达相关,包括血管内皮生长因子、基质金属蛋白酶9(MMP-9)、β-连环蛋白、E-钙黏蛋白、Snail、Twist和波形蛋白。多变量分析显示,lncRNA是疾病进展和死亡率的预后因素(风险比[HR],1.730;p = 0.043和HR,2.170;p = 0.033)。lncRNA高表达患者的无进展生存期和总生存期明显较短。
这些发现突出了lncRNA对预测SOC患者预后的临床意义,并表明其通过调节血管内皮生长因子(VEGF)、MMP-9和EMT相关机制促进肿瘤侵袭性的潜力。