LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2 in Gastric Cancer.
LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2 in Gastric Cancer.
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DOI：
10.3349/ymj.2020.61.11.923
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发表时间：
2020-11
影响因子：
2.4
通讯作者：
Lee SK
中科院分区：
文献类型：
--
作者：
Byun HJ;Yoon JH;Lee SK
Wnt/β-catenin通路信号转导和抑癌基因异常表达在胃癌中的作用机制尚不清楚。最近，长非编码RNA(LncRNA)被认为是其中的一个可能的联系。在这项研究中，我们研究了肺癌相关转录本1(LUCAT1)在GC中的作用。采用定量逆转录-聚合酶链式反应(qRT-PCR)检测LUCAT1在胃癌细胞系和100例组织标本中的表达。用两种不同的siRNAs抑制LUCAT1的表达。用四甲基偶氮唑盐比色法检测细胞存活率。为了分析转移，进行了划痕愈合试验、Matrigel侵袭试验和集落形成试验。PI/Annexin-V染色分析细胞凋亡。为了检测抑癌基因的甲基化状态，进行了甲基化特异的聚合酶链式反应。Western印迹法检测LUCAT1(SiLUCAT1)沉默后上皮-间充质转化和细胞凋亡标志物的变化。LUCAT1在胃癌细胞系和癌组织中的表达显著高于正常胃细胞和癌旁组织(p<；0.001)。与SICT相比，LUCAT1的两个不同的siRNAs减少了细胞的增殖、侵袭和迁移(p<；0.05)，并且这些减少被pcDNA-LUCAT1恢复(p<；0.05)。SiLUCAT1诱导CXXC4和SFRP2表达上调。SiLUCAT1可下调H3K27me3的表达，这种下调与CXXC4和SFRP2的甲基化有关。抑制LUCAT1上调EZH2的表达，并通过Wnt/β-catenin信号通路导致CXXC4和SFRP2去甲基化。我们的结论是，LUCAT1诱导CXXC4和SFRP2的甲基化，从而调节GC中的Wnt/β-catenin信号转导。
The mechanisms of Wnt/β-catenin pathway signaling and abnormal expression of tumor suppressor genes is not well known in gastric cancer (GC). Long non-coding RNA (lncRNA) has recently been identified as a possible link therein. In this study, we investigated the role of lung cancer associated transcript 1 (LUCAT1) in GC. The expression of LUCAT1 in GC cell lines and 100 tissue samples was examined by qRT-PCR. Two different siRNAs were used for knockdown of LUCAT1 expression. Cell viability was assessed by MTT assay. To analyze metastasis, scratch wound-healing assay, a Matrigel invasion assay, and colony formation assay were performed. Apoptosis was analyzed by PI/Annexin-V staining. To check the methylation status in tumor suppressor genes, methylation-specific PCR was carried out. Western blot was performed to detect epithelial-mesenchymal transition and apoptosis markers upon silencing of LUCAT1 (siLUCAT1). LUCAT1 expression in GC cell lines and tissues was significantly elevated, compared to that in normal gastric cells and adjacent non-tumor tissues (p<0.001). Two different siRNAs for LUCAT1 reduced cell proliferation, invasion, and migration, compared to siCT (p<0.05), and these reductions were restored by pcDNA-LUCAT1 (p<0.05). siLUCAT1 elicited upregulation of the expression of CXXC4 and SFRP2. The expression of H3K27me3 was reduced by siLUCAT1, and this reduction was correlated with methylation of CXXC4 and SFRP2. Inhibition of LUCAT1 up-regulated EZH2 expression and resulted in demethylation of CXXC4 and SFRP2 through the Wnt/β-catenin signaling pathway. We concluded that LUCAT1 induces methylation of CXXC4 and SFRP2, thereby regulating Wnt/β-catenin signaling in GC.
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影响因子：
11.5
作者：
Chase, Andrew;Cross, Nicholas C. P.
通讯作者：
Cross, Nicholas C. P.
影响因子：
3.1
作者：
Gao YS;Liu XZ;Zhang YG;Liu XJ;Li LZ
通讯作者：
Li LZ
影响因子：
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作者：
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通讯作者：
Guo RH
影响因子：
9
作者：
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影响因子：
5.6
作者：
Morlando M;Fatica A
通讯作者：
Fatica A