Decreased long noncoding RNA SPRY4-IT1 contributing to gastric cancer cell metastasis partly via affecting epithelial-mesenchymal transition.
Decreased long noncoding RNA SPRY4-IT1 contributing to gastric cancer cell metastasis partly via affecting epithelial-mesenchymal transition.
复制标题
长链非编码 RNA SPRY4-IT1 的减少部分通过影响上皮间质转化而导致胃癌细胞转移。
DOI：
10.1186/s12967-015-0595-9
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发表时间：
2015-08-04
影响因子：
7.4
通讯作者：
Liu XH
中科院分区：
文献类型：
--
作者：
Xie M;Nie FQ;Sun M;Xia R;Liu YW;Zhou P;De W;Liu XH
长链非编码rna （lncRNAs）正成为控制基本生物过程的关键调控因子，其紊乱表达与肿瘤发生有关。SPRY4- it1 （SPRY4内含子转录本1）是源自SPRY4基因内含子的lncRNA，参与多种癌症的发生。然而，SPRY4-IT1在胃癌中的表达模式和生物学功能尚不清楚。因此，我们开展了本研究，探讨SPRY4-IT1在胃癌发生中的潜在作用。采用QRT-PCR检测61对胃癌标本中SPRY4-IT1的表达。采用过表达和RNA干扰（RNAi）方法研究SPRY4-IT1的生物学功能。采用MTT法和菌落形成法评价SPRY4-IT1对细胞增殖的影响。将转染pCDNA-SPRY4-IT1的胃癌细胞注射到裸鼠体内，研究SPRY4-IT1对体内肿瘤发生和转移的影响。western blot或荧光免疫组织化学检测SPRY4-IT1靶点蛋白水平。采用ChIP法研究DNMT1对SPRY4-IT1表达的影响。采用学生t检验（双侧）检验各组间差异的显著性。胃癌组织中SPRY4-IT1表达降低，且与肿瘤大小较大、病理分期较晚、浸润深度较深及淋巴转移有关。SPRY4-IT1低表达的患者预后相对较差。DNA甲基化可能是控制SPRY4-IT1表达的关键因素。此外，SPRY4-IT1可能部分通过调节上皮-间质转化（epithelial-mesenchymal transition， EMT）过程参与胃癌细胞转移。SPRY4-IT1的低表达参与了胃癌的进展和转移，可能是胃癌患者预后不良的一种新的生物标志物。本文的在线版本（doi:10.1186/s12967-015-0595-9）包含补充材料，可供授权用户使用。
Long noncoding RNAs (lncRNAs) are emerging as key regulators governing fundamental biological processes, and their disorder expression involves in tumorigenesis. SPRY4-IT1 (SPRY4 intronic transcript 1), a lncRNA derived from an intron within SPRY4 gene, involves in multiple cancers development. However, the expression pattern and biological function of SPRY4-IT1 in gastric cancer is still not well documented. Hence, we carried out the present study to investigate the potential role of SPRY4-IT1 in gastric carcinogenesis. QRT-PCR was performed to detect the expression of SPRY4-IT1 in 61 pairs of gastric cancer samples. Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of SPRY4-IT1. The effect of SPRY4-IT1 on proliferation was evaluated by MTT and colony formation assays. Gastric cancer cells transfected with pCDNA-SPRY4-IT1 were injected into nude mice to study the effect of SPRY4-IT1 on tumorigenesis and metastasis in vivo. Protein levels of SPRY4-IT1 targets were determined by western blot or fluorescence immunohistochemistry. ChIP assays were performed to investigate the effect of DNMT1 on SPRY4-IT1 expression. Differences between groups were tested for significance using Student’s t test (two-tailed). SPRY4-IT1 expression is decreased in gastric cancer tissues and associated with larger tumor size, advanced pathological stage, deeper depth of invasion and lymphatic metastasis. Patients with lower SPRY4-IT1 expression had a relatively poor prognosis. DNA methylation may be a key factor in controlling the SPRY4-IT1 expression. Furthermore, SPRY4-IT1 contributed to gastric cancer cells metastasis might partly via regulating epithelial–mesenchymal transition (EMT) process. Low expression of SPRY4-IT1 is involved in progression and metastasis of gastric cancer and may represent a novel biomarker of poor prognosis in patients with gastric cancer. The online version of this article (doi:10.1186/s12967-015-0595-9) contains supplementary material, which is available to authorized users.