HOTAIR/miR1 axis acts as a potential chemotherapy target in gastric cancer

Abstract

Gastric cancer is one of the most common cancers in the world. Delayed diagnosis is the most common cause of death in patients. Long noncoding RNAs (lncRNAs) are a group of non-coding RNAs that are effective in the incidence of cancers. Studies in different cancers determined HOTAIR as an important lncRNA in tumorigenesis. In gastric cancer, the function of HOTAIR in the initiation and progression of cancer seems to be crucial. In this study, we confirmed the significant differential expression of HOTAIR between gastric tumors and normal tissues in different datasets. In the following, the regulatory function of HOTAIR and its interaction with miRNAs in development of gastric cancer was analyzed. Our analysis determined that the upregulation of HOTAIR is essential to different pathways associated with the progression of gastric cancer. Further analysis determined numerous miRNAs as potential targets for HOTAIR. Among them, we demonstrated miR-1 as a significant miRNA with negative correlation with HOTAIR in gastric tumors. Validation analysis determined that HOTAIR is a target of cisplatin as a common chemotherapy drug. Eventually, the effect of cisplatin on the expression of HOTAIR and its potential target, miR-1, was checked by an in vitro study. Cisplatin treatment on the gastric cancer cell line showed that there is a significant negative correlation between the downregulation of HOTAIR and the upregulation of miR-1 in treated cells. In conclusion, comprehensive in silico analysis and experimental study provided evidence for the importance of the HOTAIR/miR-1 axis as potential diagnostic and treatment strategies for gastric cancer.