H19 functions as a competing endogenous RNA to regulate human epidermal growth factor receptor expression by sequestering let‑7c in gastric cancer.

Abstract

Long non‑coding RNA (lncRNA) H19 has been suggested to serve important roles in the progression of gastric cancer (GC); however, the mechanism involved is largely unknown. The present study aimed to investigate the mechanism underlying the effect of H19 on human epidermal growth factor receptor (HER2) expression. Let‑7c belongs to the let‑7 family, which has been reported to be downregulated in cancers and considered to serve as a tumor suppressor. Let‑7c has been negatively associated with the expression of human epidermal growth factor receptor 2 (HER2). Reverse transcription‑quantitative polymerase chain reaction was used to examine the expression levels of H19 and let‑7c in GC tissues and cell lines. HER2 protein expression levels were examined using immunohistochemistry and western blot analyses. The effect of H19 on let‑7c and HER2 expression was analyzed following transfection of small interfering RNA targeting H19 in GC cells. The results indicated that the expression levels of H19 lncRNA in GC tissue samples were significantly higher when compared with that in matched benign adjacent tissue samples (P<0.001). H19‑silenced GC cells exhibited significantly increased let‑7c expression and decreased HER2 protein expression levels. Assessment of tumor diameter and pathological tumor stage suggested that increased H19 expression was associated with a poorer prognosis in patients with GC. The results of the present study suggest that H19 may function as a competing endogenous RNA to regulate HER2 expression by sequestering let‑7c in GC cells. The present study has aided the understanding of the mechanism of H19 lncRNA in GC, and has provided evidence for the application of lncRNA‑based diagnostic and therapeutic strategies for GC.