Association of HOTAIR expression with PI3K/Akt pathway activation in adenocarcinoma of esophagogastric junction

Abstract

Objectives: Although the Hox transcript antisense intergenic RNA (HOTAIR), a vital long non-coding RNA, is known to participate in the development and progression of a wide range of carcinomas, there are still no published reports regarding its expression in adenocarcinoma of esophagogastric junction (AEJ). The aims of this study were to investigate the expression of HOTAIR, and to analyze the association of its expression with PI3K/Akt pathway activation in clinical AEJ patients.

Methods: Nine normal epithelial tissues and 41 samples of AEJ were studied comparably. The expression of HOTAIR was detected by real-time PCR according to the different tumor grades in these AEJ tissues. Western blot was performed to reveal the Ser473-phosphorylated Akt and total Akt levels. Results: HOTAIR was found to be up-regulated in higher grades of AEJ tissues compared to low grades and/or noncancerous tissues. pAkt expression was also found to be up-regulated in tissues of higher tumor stages. We found that the overexpression of HOTAIR finely correlated with elevated Ser473-phosphorylated Akt levels. Conclusion: Upregulated HOTAIR was associated with abnormal activated PI3K/Akt pathway, which might serve as a promising therapeutic strategy for AEJ treatment.

Keywords: AEJ; HOTAIR; PI3K/Akt pathway.

Figure 1

HOTAIR expression is upregulated in adenocarcinoma of esophagogastric junction (WHO grade I to IV) tissues. Compared with non-tumor tissue (Normal, n=9), AEJ tissues of WHO grade I (n=8), grade II (n=9), grade III (n=14) and grade IV (n=10), tissues from AEJ (n=41) displayed higher HOTAIR expression as determined by real-time PCR. GAPDH was used as internal control. Different grades were showed in different colors. *: P<0.05, **: P<0.01, ***: P<0.001 (One-Way ANOVA).

Figure 2

Level of pAkt is upregulated in adenocarcinoma of esophagogastric junction (WHO grade I to IV) tissues. (A) Western blot results of pAkt and tAkt in normal and tumor tissues with different grades, representatively. (B) Compared with non-tumor tissue (Normal, n=9), AEJ tissues of WHO grade I (n=8), grade II (n=9), grade III (n=14) and grade IV (n=10), tissues from AEJ (n=41) displayed higher ratio of pAkt/tAkt expression as determined by western blot. Different grades were showed in different colors. *: P<0.05, **: P<0.01, ***: P<0.001 (One-Way ANOVA).

Figure 3

Spearman’s correlation analysis between HOTAIR expression and the pAkt levels. The positive correlation between HOTAIR expression and pAkt in 41 AEJ samples was determined using Spearman’s correlation analysis (P=0.0001).