Long noncoding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene. However, the underlying mechanism of UCA1 in the development of gastric cancer is not fully understood. In the present study, we aimed to identify how UCA1 promotes gastric cancer development. The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to analyze UCA1 and myosin VI (MYO6) expression in gastric cancer. Western blot and quantitative real-time PCR (QPCR) were performed to test the expression level of the UCA1/miR-145/MYO6 axis in gastric cancer cell lines and tissues. The roles of the UCA1/miR-145/MYO6 axis in gastric cancer in vitro and in vivo were investigated by CCK-8 assay, flow cytometry, siRNAs, immunohistochemistry, and a mouse xenograft model. The targeted relationship among UCA1, miR-145, and MYO6 was predicted using LncBase Predicted v.2 and TargetScan online software, and then verified by luciferase activity assay and RNA immunoprecipitation. UCA1 expression was higher but miR-145 expression was lower in gastric cancer cell lines or tissues, compared to the adjacent normal cell line or normal tissues. Function analysis verified that UCA1 promoted cell proliferation and inhibited cell apoptosis in the gastric cancer cells in vitro and in vivo. Mechanistically, UCA1 could bind directly to miR-145, and MYO6 was found to be a downstream target gene of miR-145. miR-145 mimics or MYO6 siRNAs could partly reverse the effect of UCA1 on gastric cancer cells. UCA1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-145 to upregulate MYO6 expression in gastric cancer, indicating that the UCA1/miR-145/MYO6 axis may serve as a potential therapeutic target for gastric cancer.

中文翻译：

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LncRNA UCA1通过miR-145/MYO6轴促进胃癌的发展

长链非编码 RNA (lncRNA)、尿路上皮癌相关 1 (UCA1) 在多种癌症中异常表达，并已被证实为癌基因。然而，UCA1在胃癌发展中的潜在机制尚不完全清楚。在本研究中，我们旨在确定 UCA1 如何促进胃癌的发展。癌症基因组图谱 (TCGA) 和基因型组织表达 (GTEx) 数据用于分析胃癌中 UCA1 和肌球蛋白 VI (MYO6) 的表达。进行蛋白质印迹和定量实时PCR（QPCR）以测试UCA1 / miR-145 / MYO6轴在胃癌细胞系和组织中的表达水平。通过CCK-8测定、流式细胞术、siRNA、免疫组织化学和小鼠异种移植模型研究了UCA1/miR-145/MYO6轴在体外和体内胃癌中的作用。使用 LncBase Predicted v.2 和 TargetScan 在线软件预测 UCA1、miR-145 和 MYO6 之间的靶向关系，然后通过荧光素酶活性测定和 RNA 免疫沉淀验证。与邻近的正常细胞系或正常组织相比，胃癌细胞系或组织中的 UCA1 表达较高，但 miR-145 表达较低。功能分析证实UCA1在体外和体内促进胃癌细胞增殖并抑制细胞凋亡。机制上，UCA1 可以直接与 miR-145 结合，发现 MYO6 是 miR-145 的下游靶基因。miR-145 模拟物或 MYO6 siRNA 可以部分逆转 UCA1 对胃癌细胞的作用。