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.
Keywords: Gastric cancer; HYPAL; Hypoxia; Proliferation; lncRNAs.
© 2021. The International Gastric Cancer Association and The Japanese Gastric Cancer Association.