Long non-coding RNA XLOC_000647 suppresses progression of pancreatic cancer and decreases epithelial-mesenchymal transition-induced cell invasion by down-regulating NLRP3.
Long non-coding RNA XLOC_000647 suppresses progression of pancreatic cancer and decreases epithelial-mesenchymal transition-induced cell invasion by down-regulating NLRP3.
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DOI：
10.1186/s12943-018-0761-9
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发表时间：
2018-01-31
期刊：
影响因子：
37.3
通讯作者：
Jiang K
中科院分区：
文献类型：
--
作者：
Hu H;Wang Y;Ding X;He Y;Lu Z;Wu P;Tian L;Yuan H;Liu D;Shi G;Xia T;Yin J;Cai B;Miao Y;Jiang K
长链非编码RNA（lncRNA）在包括胰腺癌（PC）在内的多种肿瘤的发生和发展中起重要作用。最近的研究表明，lncRNA可以“顺式”调节其邻近基因的表达。在此之前，我们使用lncRNA微阵列鉴定了一种新的lncRNA，称为XLOC_000647，它在PC组织中下调。然而，XLOC_000647在PC中的表达和功能尚不清楚。采用实时荧光定量PCR检测XLOC_000647和NLRP 3在PC标本和细胞系中的表达。用Transwell法测定PC细胞的迁移和侵袭。Western blot检测PC细胞中上皮间质转化（EMT）标志物的表达。在体外和体内评估了XLOC_000647对PC细胞的影响。体外研究了NOD样受体家族pyrin domain-containing 3（NLRP 3）在PC中的功能。此外，在体外检查了XLOC_000647对PC中NLRP 3的调节。在此，XLOC_000647表达在PC组织和细胞系中下调。XLOC_000647的表达水平与肿瘤分期、淋巴结转移和总生存期显著相关。XLOC_000647的过表达在体外减弱了细胞增殖、侵袭和EMT，并在体内损害了肿瘤生长。此外，在体外和体内观察到XLOC_000647水平与其基因组附近基因NLRP 3之间存在显著负相关性。此外，XLOC_000647通过抑制NLRP 3的启动子活性来降低NLRP 3。在体外，NLRP 3的敲低降低了癌细胞的增殖、侵袭和EMT。重要的是，在XLOC_000647过表达后，细胞侵袭和EMT的相应表型被NLRP 3的过表达逆转。总之，这些结果表明XLOC_000647作为lncRNA的新型肿瘤抑制因子发挥作用，并作为NLRP 3的重要调节因子，抑制PC中的细胞增殖、侵袭和EMT。
Long non-coding RNAs (lncRNAs) play an important role in the development and progression of various tumors, including pancreatic cancer (PC). Recent studies have shown that lncRNAs can ‘act in cis’ to regulate the expression of its neighboring genes. Previously, we used lncRNAs microarray to identify a novel lncRNA termed XLOC_000647 that was down-regulated in PC tissues. However, the expression and function of XLOC_000647 in PC remain unclear. The expression of XLOC_000647 and NLRP3 in PC specimens and cell lines were detected by quantitative real-time PCR. Transwell assays were used to determine migration and invasion of PC cells. Western blot was carried out for detection of epithelial-mesenchymal transition (EMT) markers in PC cells. The effect of XLOC_000647 on PC cells was assessed in vitro and in vivo. The function of NOD-like receptor family pyrin domain-containing 3 (NLRP3) in PC was investigated in vitro. In addition, the regulation of NLRP3 by XLOC_000647 in PC was examined in vitro. Here, XLOC_000647 expression was down-regulated in PC tissues and cell lines. The expression level of XLOC_000647 was significantly correlated to tumor stage, lymph node metastasis, and overall survival. Overexpression of XLOC_000647 attenuated cell proliferation, invasion, and EMT in vitro and impaired tumor growth in vivo. Further, a significantly negative correlation was observed between XLOC_000647 levels and its genomic nearby gene NLRP3 in vitro and in vivo. Moreover, XLOC_000647 decreased NLRP3 by inhibiting its promoter activity. Knockdown of NLRP3 decreased proliferation of cancer cells, invasion, and EMT in vitro. Importantly, after XLOC_000647 was overexpressed, the corresponding phenotypes of cells invasion and EMT were reversed by overexpression of NLRP3. Together, these results indicate that XLOC_000647 functions as a novel tumor suppressor of lncRNA and acts as an important regulator of NLRP3, inhibiting cell proliferation, invasion, and EMT in PC.
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