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首页> 外文期刊>Cell cycle >Long non-coding RNA Linc00152 is involved in cell cycle arrest, apoptosis, epithelial to mesenchymal transition, cell migration and invasion in gastric cancer
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Long non-coding RNA Linc00152 is involved in cell cycle arrest, apoptosis, epithelial to mesenchymal transition, cell migration and invasion in gastric cancer

机译:长非编码RNA Linc00152参与胃癌的细胞周期停滞,凋亡,上皮向间质转化,细胞迁移和侵袭

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Gastric cancer remains a serious threat to public health with high incidence and mortality worldwide. Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play important roles in regulating gene expression and are involved in various pathological processes, including gastric cancer. To investigate the possible role of dysregulated lncRNAs in gastric cancer development, we performed lncRNA microarray and identified 3141 significantly differentially expressed lncRNAs in gastric cancer tissues. Next, some of deregulated lncRNAs were validated among about 60 paired gastric cancer specimens such as Linc00261, DKFZP434K028, RPL34-AS1, H19, HOTAIR and Linc00152. Our results found that the decline of DKFZP434K028 and RPL34-AS1, and the increased expression of Linc00152 positively correlated with larger tumor size. The high expression levels of HOTAIR were associated with lymphatic metastasis and poor differentiation. Since the biological roles of Linc00152 are largely unknown in gastric cancer pathogenesis, we assessed its functions by silencing its up-regulation in gastric cancer cells. We found that Linc00152 knockdown could inhibit cell proliferation and colony formation, promote cell cycle arrest at G1 phase, trigger late apoptosis, reduce the epithelial to mesenchymal transition (EMT) program, and suppress cell migration and invasion. Taken together, we delineate the gastric cancer lncRNA signature and demonstrate the oncogenic functions of Linc00152. These findings may have implications for developing lncRNA-based biomarkers for diagnosis and therapeutics for gastric cancer.
机译:胃癌仍然是对公众健康的严重威胁,全世界的发病率和死亡率很高。越来越多的证据表明,长的非编码RNA(lncRNA)在调节基因表达中起重要作用,并参与包括胃癌在内的各种病理过程。为了研究失调的lncRNA在胃癌发展中的可能作用,我们进行了lncRNA基因芯片分析,并鉴定了在胃癌组织中3141个差异显着表达的lncRNA。接下来,在大约60个配对的胃癌标本中验证了一些失调的lncRNA,例如Linc00261,DKFZP434K028,RPL34-AS1,H19,HOTAIR和Linc00152。我们的结果发现DKFZP434K028和RPL34-AS1的减少以及Linc00152的表达增加与更大的肿瘤大小正相关。 HOTAIR的高表达水平与淋巴转移和分化差有关。由于Linc00152的生物学作用在胃癌的发病机理中很大程度上是未知的,因此我们通过沉默其在胃癌细胞中的上调来评估其功能。我们发现Linc00152基因敲低可以抑制细胞增殖和集落形成,促进细胞周期停滞在G1期,触发晚期细胞凋亡,减少上皮到间充质转化(EMT)程序,并抑制细胞迁移和侵袭。两者合计,我们描绘了胃癌lncRNA签名,并证明了Linc00152的致癌功能。这些发现可能对开发用于胃癌的诊断和治疗的基于lncRNA的生物标记物有影响。

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