LncRNA HOTAIR promotes gastric cancer proliferation and metastasis via targeting miR-126 to active CXCR4 and RhoA signaling pathway.

Abstract

HOTAIR, a well‐known long noncoding RNAs (lncRNA), has been recognized to contribute to the tumor metastasis in several tumors. But its role in gastric cancer remains elusive. Here, we reported an increase in HOTAIR promoted proliferation and metastasis of gastric cancer cell lines. The HOTAIR and miR‐126 level was determined in 15 paired primary gastric cancer tissues and their adjacent noncancerous gastric tissues. Over‐expression or downregulation HOTAIR was conducted in AGS or BGC‐823 cells to investigate the impact of HOTAIR in proliferation and metastasis. Then dual luciferase reporter assay was utilized to study the interaction between CXCR4 and miR‐126. Cells transfected with shHOTAIR or miR‐126 mimic were subjected to western blot to investigate the role of SDF‐1/CXCR4 signaling in HOTAIR mediated proliferation and metastasis. HOTAIR was highly expressed in gastric cancer tissues and several gastric cancer cell lines. Overexpressed HOTAIR facilitated proliferation and metastasis in vitro while HOTAIR knockdown inhibit proliferation and metastasis. A negative correlation was observed between miR‐126 and HOTAIR. And, we also confirmed the decrease in miR‐126 in clinic specimen. Furthermore, HOTAIR and miR‐126 negatively regulated each other and then increase or decrease CXCR4 expression and downstream pathway, respectively. CXCR4 was confirmed as a direct target of miR‐126. Our study demonstrated that high HOTAIR expression promote proliferation and metastasis in gastric cancer via miR‐126/CXCR4 axis and downstream signaling pathways.