The Regulatory Effect of HOTAIR on the Protein and RNA Levels of ZEB1 and Its Potential Role in the EMT Process

Abstract

Background: Invasion and metastasis in tumors are considered as two most important reasons for the reduction of treatment efficiency, as well as an increase in the mortality rate among the patients. According to the evidence, HOX transcript antisense RNA (HOTAIR) accounts for one of the main IncRNAs associated with the development and expansion of gastric cancer (GC). Objectives: This research investigates the impact of HOTAIR suppression on the expression and translation of the ZEB1 marker in GC. Methods: The knockdown HOTAIR was in the AGS cell line using small interfering RNA targeting against HOTAIR (si-HOTAIR). The impact of HOTAIR expression on the cell proliferation was previously evaluated by the MTT assay. The expression of the zinc finger E-box binding homeobox 1 (ZEB1) gene in transfected cell lines was quantified compared to the control samples using the quantitative real-time polymerase chain reaction (qRT-PCR). The enzyme-linked immunosorbent assay (ELISA) was also used to assess the HOTAIR suppression impact on the ZEB1 protein. Results: The findings revealed that a decrease in the HOTAIR expression could cause a reduction in the proliferation and growth of cancer cells (Fold changes = 0/28, P-value < 0.01). According to the impact of changes in the HOTAIR expression levels on the ZEB1 expression, the ZEB1 expression level was directly correlated with HOTAIR so that a decrease in the HOTAIR expression led to a significant decline in the ZEB1 expression level (P-value < 0.05). At the protein level, the effect of the knockdown of HOTAIR expression on the reduction of ZEB1 protein was also observed. Conclusions: Our findings showed a significant association between the HOTAIR and ZEB1 expression levels. Overall, the HOTAIR-ZEB1 axis plays a vital role in the epithelial-to-mesenchymal transition (EMT) process in human GC and represents a new therapeutic strategy for future GC treatment.