Immunopharmacol Immunotoxicol. 2022 Jun 23;1-13.doi: 10.1080/08923973.2022.2078727. Online ahead of print. (IF2.73)

LncRNA DLEU2 silencing impedes the migration, invasion and EMT in gastric cancer cell by suppressing PI3K/AKT signaling pathway

Jun Hu  1 Mingyun Wang  1 Yang Yang  2 Yajun Xing  1 Shuanggen Li  1



Context: The high expression of long non-coding RNA deleted in lymphocytic leukaemia 2 (lncRNA DLEU2) has been confirmed in gastric cancer (GC).Objective: However, the detailed mechanism concerning its involvement in GC remained unclear, which we aimed to explore in this study.Materials and methods: LncRNA DLEU2 expression in GC was estimated by bioinformatic analysis, and the relationship between the expression of DLEU2 and the clinicopathological characteristics of patients with GC was performed. qRT-PCR was employed to detect the expression of lncRNA DLEU2 and confirm the transfection efficiency following the knockdown or overexpression of DLEU2. Functional assays, including CCK-8, flow cytometry, scratching test and Transwell assays, were used to determine the role of DLEU2 in tumor phenotypes. The effects of DLEU2 on the PI3K/Akt pathway were detected by western blot. For elucidating the functions of DLEU2/PI3K/Akt axis in GC, we inhibited the PI3K/Akt pathway in rescue experiments, and evaluated the expression levels of epithelial-mesenchymal transition (EMT)-related proteins by western blot.Results: The expression of DLEU2 was aberrantly up-regulated in GC tissues and cells, which was correlated with the degree of tumor differentiation, cancer antigen 19-9 (CA19-9) and Lauren histologic classification of patients with GC. Silencing of DLEU2 induced apoptosis, attenuated viability, migration and invasion as well as inhibited the PI3K/Akt signaling pathway in GC cells. Mechanistically, the DLEU2/PI3K/Akt axis promoted the progression of GC and the EMT by down-regulating the expression of E-Cadherin and up-regulating those of N-Cadherin and Vimentin.Discussion and conclusions: LncRNA DLEU2 promoted the migration, invasion and EMT in GC by activating the PI3K/Akt pathway.

Keywords: Long non-coding RNA deleted in lymphocytic leukemia 2; PI3K/Akt signaling pathway; epithelial-mesenchymal transition; gastric cancer; metastasis.