Abstract
BackgroundGastric cancer (GC) remains an important cancer worldwide. Further understanding of the molecular mechanisms of gastric carcinogenesis will enhance the diagnosis and treatment of GC.MethodsThe expression of DLEU2 and ETS2 was analyzed in several GC cell lines using GEPIA online analyze, qRT-PCR and immunohistochemistry. The biological behavior of GC cells was detected by CCK8, clone formation, transwell, wound healing, western blot, and flow cytometry assay. More in-depth mechanisms were studied.ResultsDLEU2 was significantly up-regulated in GC tissues and cell lines. The expression of DLEU2 was significantly associated with pathological grading and TNM stage of GC patients. Furthermore, knockdown of DLEU2 inhibited the proliferation, migration, and invasion of AGS and MKN-45 cells, while overexpression of DLEU2 promoted the proliferation, migration, and invasion of HGC-27 cells. MiR-30a-5p could directly bind to the 3’ UTR region of ETS2. Moreover, DLEU2 bound to miR-30a-5p through the same binding site, which facilitated the expression of ETS2. Knockdown of DLEU2 reduced the protein level of intracellular ETS2 and inhibited AKT phosphorylation, while overexpression of DLEU2 induced the expression of ETS2 and the phosphorylation of AKT. ETS2 was highly expressed in GC tissues. The expression of ETS2 was significantly associated with age, pathological grading, and TNM stage. ETS2 overexpression promoted cell proliferation and migration of AGS and MKN-45 cells. Furthermore, ETS2 overexpression rescued cell proliferation and migration inhibition induced by DLEU2 down-regulation and miR-30a-5p up-regulation in AGS and MKN-45 cells.ConclusionsDLEU2 is a potential molecular target for GC treatment.
Highlights
Gastric cancer (GC) remains an important cancer worldwide
DLEU2 is up‐regulated in GC tissues and cell lines GEPIA collected the RNA expression information of 408 stomach adenocarcinoma (STAD) and 211 normal tissues
Statistical analysis showed that the expression of DLEU2 was significantly associated with the pathological grading (P = 0.0087) and TNM stage (P = 0.0382) of GC patients (Table 1)
Summary
Gastric cancer (GC) remains an important cancer worldwide. Sequence, and function, ncRNAs are divided into various subcategories, Han et al Cancer Cell Int (2021) 21:376 the two most famous of which are long-noncoding RNAs (lncRNAs) and microRNAs (miRNAs). LncRNAs can interact with proteins, DNA, and RNA through epigenetic modification, transcription, and post-transcriptional regulation, thereby playing an indispensable role in cells [7]. LncRNAs can play the role of competitive endogenous RNAs (ceRNAs), which regulate the expression of target genes through competitive binding with miRNAs and are closely related to tumor progression [11, 12]. LncRNAs are expected to be biomarkers for the diagnosis and prognosis of GC, but the underlying mechanism remains to be clarified [13]
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