Wang Shuai, Liu Feng, Deng Junji, Cai Xinsheng, Han Junqing, Liu Qi
1 Department of Clinical Medicine, Shandong University , Jinan, Shandong, China .
2 Department of Oncology, Weifang Traditional Chinese Hospital , Weifang, Shandong, China .
Cell Reprogram. 2016 Oct;18(5):319-326. doi: 10.1089/cell.2016.0001. Epub 2016 Sep 7.
Gastric cancer remains an incurable malignance and the second leading cause of cancer death globally. Recent progress in gastric cancer research has demonstrated the crucial roles of cancer stem cells (CSCs) in the development, metastasis, and drug resistance of this disease. Various studies have highlighted the role of long noncoding RNAs (lncRNAs) in the pathogenesis of gastric cancer. In this study, through fluorescence-activated cell sorting, we isolated gastric CSCs (GCSCs) from MKN-45 cells and demonstrated for the first time that lncRNA ROR was highly expressed in CD133 GCSCs. Overexpression of lncRNA ROR significantly increased, but knockdown of lncRNA ROR inhibited the proliferation and invasion of GCSCs. Most importantly, lncRNA ROR led to upregulation of several key stemness transcriptional factors, such as OCT4, SOX2, and NANOG, as well as CD133 GCSC. Our data demonstrated that lncRNA ROR was associated with core stemness transcriptional factors and the pluripotent state of GCSCs. These results further improved our understanding of the functional cross talking network during development of GCSCs and may provide novel target for the diagnostics and therapeutics of gastric cancer.
胃癌仍然是一种无法治愈的恶性肿瘤，是全球癌症死亡的第二大主要原因。胃癌研究的最新进展表明，癌症干细胞（CSCs）在这种疾病的发生、转移和耐药性中起着关键作用。各种研究都强调了长链非编码RNA（lncRNAs）在胃癌发病机制中的作用。在本研究中，我们通过荧光激活细胞分选从MKN-45细胞中分离出胃癌症干细胞（GCSCs），并首次证明lncRNA ROR在CD133 GCSCs中高表达。lncRNA ROR的过表达显著增加，但lncRNA ROR的敲低抑制了GCSCs的增殖和侵袭。最重要的是，lncRNA ROR导致几种关键的干性转录因子上调，如OCT4、SOX2和NANOG，以及CD133 GCSC。我们的数据表明，lncRNA ROR与核心干性转录因子以及GCSCs的多能状态有关。这些结果进一步加深了我们对GCSCs发育过程中功能相互作用网络的理解，并可能为胃癌的诊断和治疗提供新的靶点。
