Essential meiotic structure-specific endonuclease1 ( EME1) promotes malignant features in gastric cancer cells via the Akt/GSK3B/CCND1 pathway

ABSTRACT

DNA damage plays a key role in various biological processes involved in malignant disease, the role of the DNA damage repair gene EME1 (essential meiotic structure-specific endonuclease 1) in gastric cancer (GC) development is unknown. This work aimed to investigate expression and role of EME1 in tumorigenesis. Quantitative real-time polymerase chain reaction (qRT-PCR), immunoblot, cell viability and dual-luciferase reporter assays, RNAi and gene transfection, and immunofluorescent staining were performed to assess EME1 regulation in GC tumorigenesis. Further, mouse xenografts were established for in vivo mechanistic studies. EME1 was found to be upregulated in both gastric cancer cells and clinically obtained tumors. Additionally, EME1 levels were strongly associated with the differentiation level of GC and lymph node metastasis. In vivo and in vitro knockdown of EME1 markedly suppressed the proliferative, migratory, and invasive abilities of GC cells and enhanced apoptotic cell death and cell cycle arrest rates. Mechanistically, EME1 modulated Akt/GSK3B/CCND1 signaling. MYB may also have contributed to EME1-dependent gastric carcinogenesis. Elevated EME1 expressions may enhance the proliferative and metastatic abilities of GC cells, thereby acting as a tumor-promoting factor via Akt. These findings reveal that EME1 is an important biomarker for GC prognosis and treatment in humans.

Abbreviations: Essential meiotic structure-specific endonuclease 1 ( EME1); MYB proto-oncogene ( MYB); Cell counting kit-8 (CCK-8); 4,6-diamimo-2-phenyl indole (DAPI); Quantitative real-time PCR (qRT-PCR); Gastric cancer (GC); Immunofluorescence (IF); Small interfering RNA (siRNA); Small hairpin RNA (shRNA); Alpha serine threonine-protein kinase (Akt); Glycogen synthase kinase 3 beta (GSK3B); Cyclin D1 (CCND1); Glyceraldehyde-3-phosphate dehydrogenase (GAPDH); Disease-free survival (DFS); Overall survival (OS); Negative controls (NC); American Joint Committee on Cancer (AJCC); Coding sequence (CDS); Lymph node metastasis (LNM); Tris-Buffered Saline-Tween-20 (TBST); Horseradish Peroxidase (HRP); Electrochemiluminescence (ECL); Polyvinylidene Fluoride (PVDF); Excision repair cross complementation group 1 (ERCC1).