Gastric cancer (GC) is a common malignant solid tumor that is characterized by high hypoxia. The transcription of genes associated with hypoxia affects tumor occurrence and development. Long non-coding RNAs (lncRNAs) have been reported to play important roles in cancer development. In this study, we screened for differentially expressed ncRNAs (non-coding RNA) and mRNAs between hypoxia-inducible factor-1 (HIF-1α) knockdown GC cells and scrambled GC cells. Microarray data revealed that HIF-1α regulated the expression of LINC01355 (Hypoxia Yield Proliferation Associated LncRNA, HYPAL). HYPAL was found to be significantly upregulated in GC cells and tissues and was correlated with poor GC prognosis. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays revealed that HIF-1α promoted HYPAL expression by binding the promoter region. A regulatory network for the competing endogenous RNA (ceRNA) was constructed using bioinformatics tools. Mechanistic studies revealed that HYPAL acted as a ceRNA of miR-431-5p to regulate CDK14 expression. Carcinogenic effects of HYPAL were evaluated in vitro and in vivo. The HIF-1α/HYPAL/miR-431-5p/CDK14 (Cyclin-dependent kinase 14) axis activated the Wnt/β-catenin signaling pathway and induced GC cell proliferation while inhibiting apoptosis. In conclusion, HYPAL is a potential molecular target for GC therapy.

胃癌（gastric cancer，GC）是一种以高缺氧为特征的常见恶性实体瘤。与缺氧相关的基因转录影响肿瘤的发生和发展。据报道，长链非编码 RNA (lncRNA) 在癌症发展中发挥重要作用。在本研究中，我们筛选了低氧诱导因子 1 (HIF-1α) 敲低 GC 细胞和乱序 GC 细胞之间差异表达的 ncRNA（非编码 RNA）和 mRNA。微阵列数据显示，HIF-1α 调节 LINC01355（Hypoxia Yield Proliferation Associated LncRNA，HYPAL）的表达。发现 HYPAL 在 GC 细胞和组织中显着上调，并且与 GC 预后不良相关。染色质免疫沉淀 (ChIP) 和荧光素酶报告基因分析表明，HIF-1α 通过结合启动子区域促进 HYPAL 表达。使用生物信息学工具构建了竞争性内源性 RNA (ceRNA) 的监管网络。机制研究表明，HYPAL 作为 miR-431-5p 的 ceRNA 来调节 CDK14 的表达。在体外和体内评估了 HYPAL 的致癌作用。HIF-1α/HYPAL/miR-431-5p/CDK14（细胞周期蛋白依赖性激酶 14）轴激活Wnt/β-catenin信号通路和诱导 GC 细胞增殖同时抑制细胞凋亡。总之，HYPAL 是 GC 治疗的潜在分子靶点。