J Gastric Cancer.  2020 Jun;20(2):139-151. 10.5230/jgc.2020.20.e12.

LETM1 Promotes Gastric Cancer Cell Proliferation, Migration, and Invasion via the PI3K/Akt Signaling Pathway

• Zhang Y
• Chen L
• Cao Y
• Chen S
• Xu C
• Xing J
• Zhang K

• KMID: 2503596
• DOI: http://doi.org/10.5230/jgc.2020.20.e12

Abstract

Purpose
Globally, there is a high incidence of gastric cancer (GC). Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is reported to play a vital role in several human malignancies. However, there is limited understanding of the role of LETM1 in GC. This study aims to investigate the effects of LETM1 on proliferation, migration, and invasion of GC cells.
Materials and Methods
The expression levels of LETM1 in the normal gastric mucosal epithelial cells (GES-1) and GC cells were analyzed by quantitative real-time polymerase chain reaction and western blotting. CCK-8, wound healing, and Transwell invasion assays were performed to evaluate the effect of LETM1 knockdown or overexpression on the proliferation, migration, and invasion of the GC cells, respectively. Additionally, the effect of LETM1 knockdown or overexpression on GC cell apoptosis was determined by flow cytometry. Furthermore, the effect of LETM1 knockdown or overexpression on the expression levels of PI3K/Akt signaling pathway-related proteins was evaluated by western blotting.
Results
The GC cells exhibited markedly higher mRNA and protein expression levels of LETM1 than the GES-1 cells. Additionally, the knockdown of LETM1 remarkably suppressed the GC cell proliferation, migration, and invasion, and promoted the apoptosis of GC cells, which were reversed upon LETM1 overexpression. Furthermore, the western blotting analysis indicated that LETM1 facilitates GC progression via the PI3K/Akt signaling pathway.
Conclusions
LETM1 acts as an oncogenic gene to promote GC cell proliferation, migration, and invasion via the PI3K/Akt signaling pathway. Therefore, LETM1 may be a potential target for GC diagnosis and treatment.

Keyword

LETM1 protein, human; Phosphatidylinositol 3 kinase; Protein kinase B; Stomach neoplasms