LETM1 Promotes Cell Proliferation,migration And Invasion Via The PI3K/Akt Signaling Pathway In Gastric Cancer

Background Gastric cancer is one of the common malignant tumors of the digestive system.Because its early symptoms are not obvious and it lacks specific diagnostic indicators,it is often in the middle and advanced stages when it is discovered.The key to improving long-term survival for patients.Leucine zipper / EF-hand Containing Transmembrane protein 1(LETM1)is a mitochondrial inner membrane protein that is located in the broken arm of human chromosome 4.LETM1 affects mitochondrial function and thus affects cell metabolism.Previous research by our experimental group showed increased expression of LETM1 in gastric cancer tissue,but its effect on gastric cancer cell function and its mechanism are not clear.Objective To investigate the effects of leucine zipper/EF-hand containing transmembrane protein 1(LETM1)on proliferation,migration and invasion of gastric cancer(GC)cells.Methods The expressions of LETM1 in normal gastric mucosal epithelial cells GES1 and GC cells(MGC-803,AGS and MKN-45)were detected by PCR and Western blot.Next,we used CCK-8 assay and colony formation assay to measure the proliferation ability of cells,wound healing assay to assess the migration ability of cells and transwell invasion assay was utilized to evaluate the invasive ability of cells.At the same time,the effect of LETM1 on apoptosis was tested by flow cytometry.After knockdown or overexpression of LETM1,the changes of PI3K/Akt signaling pathway-related proteins were detected by Western blot.Results(1)At the RNA and protein levels,the expression of LETM1 in GC cells(MGC-803,AGS and MKN-45)was significantly higher than that in gastric epithelial cells(GES1).(2)We found that knockdown of LETM1 could significantly suppressed the proliferation,migration and invasion ability of GC cells,and facilitated the apoptosis in GC cells.Reciprocally,the contrary results could be presented in the overexpression of LETM1.(3)Western blot analysis confirmed that LETM1 plays a regulatory role through the PI3K/Akt signaling pathway.Conclusions LETM1 acts as an oncogenic gene to promote cells proliferation,migration and invasion in GC through the PI3K/Akt signaling pathway.Hence,LETM1 may serve as a potential target for GC diagnosis and treatment.