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Worldwide, the incidence rate of gastric cancer ranks fifth, and the mortality rate of gastric cancer ranks third among all malignant tumors. However, the pathogenesis of gastric cancer remains poorly understood. In this study, we demonstrated that the expression level of NELFE is higher in human gastric cancer tissues than in adjacent nontumor tissues. A high level of NELFE is associated with worse postoperative overall survival (OS) and relapse-free survival (RFS) rates in patients with gastric cancer. Moreover, the expression of NELFE is correlated with high tumor grade and lymph node metastasis in gastric cancer patients. Knockdown of NELFE dramatically inhibits the cell proliferation and metastasis of gastric cancer xenografts in vivo. Furthermore, we found that NELFE binding to the 3'UTR of E2F2 affects the mRNA stability of E2F2 to regulate the expression level of E2F2. In gastric cancer, E2F2 also acts as an oncogene to inhibit the proliferation and migration of gastric cancer cells by knocking down the expression level of E2F2. However, overexpressing E2F2 in cells with NELFE knockdown significantly reverses the inhibition of cell proliferation and migration induced by NELFE knockdown. Therefore, NELFE at least partially functions as an oncogene through E2F2. Moreover, CIBERSORTx analysis of the proportion of tumor-infiltrating immune cells (TICs) revealed that immune cells are correlated with NELFE and E2F2 expression, suggesting that NELFE and E2F2 might be responsible for the preservation of the immunodominant status for gastric cancer. In conclusion, NELFE acts as an oncogene in gastric cancer and can be used as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Abnormal gene expression is an established cause of gastric cancer (GC) initiation and progression. In this study, we aimed to identify several key genes that could be used to effectively predict progression and prognosis in patients with GC. The Cancer Genome Atlas and the Gene Expression Omnibus database were used to identify candidate genes. Fourteen genes were found to associate highly with progress, metastasis, and survival of GC. Five of these genes were overexpressed in tumor tissue compared to adjacent normal tissue. This was confirmed by reverse transcription‐polymerase chain reaction and western blotting for myosin‐Va (MYO5A), phospholipid transfer protein (PLTP), and tripeptidyl peptidase 1 (TPP1), while the CCK8 assay was used to show that these three genes promote GC cell proliferation. In summary, we demonstrate that MYO5A, PLTP, and TPP1 expression may be suitable markers for the progression and prognosis of GC. [ABSTRACT FROM AUTHOR]

Background and Aim: Gastric cancer (GC), a prevalent tumor, exerts a major economic burden, and we aimed to explore miR‐876‐3p's effects on GC and related mechanisms. Methods: Cell viability was analyzed via CCK‐8 and colony formation assay. Stem cell‐like properties were examined via spheroid colony formation assay. mRNA abundance of key genes was analyzed via quantitative polymerase chain reaction. Protein level of TMED3 and stem cell markers was examined by western blot. TargetScan, luciferase, and biotin‐miRNA pulldown assay were used to identify miR‐876‐3p's target. Results: MiR‐876‐3p was downregulated in GC, and its mRNA level had negative relationship with cisplatin resistance of GC. Moreover, decreased miR‐876‐3p expression level suggested poor prognosis of GC patients. MiR‐876‐3p inhibited drug resistance of cisplatin‐resistant cell line SGC‐7901/DDP and MKN‐45/DDP, as shown by decreased cell viability, IC50, and colony formation ability. MiR‐876‐3p inhibited stem cell‐like features and downregulated the expressions of Sox‐2, Oct‐4, CD133, and CD44 in GC cells. Luciferase and biotin‐miRNA pulldown assay confirmed that TMED3 was miR‐876‐3p's direct target. TMED3 siRNA inhibited miR‐876‐3p's effects on cisplatin resistance and stem cell‐like features of SGC‐7901/DDP cells. Conclusion: MiR‐876‐3p enhanced cisplatin sensitivity and restricted stem cell‐like features of GC through targeting TMED3. [ABSTRACT FROM AUTHOR]

Survival rates for patients with gastric cancer, especially the advanced form, remain poor and the development of targeted treatments is hampered by a lack of efficient biological targets. Poly(rC) binding protein 2 (PCBP2) is an RNA‐binding protein that contributes to mRNA stabilization, translational silencing and enhancement and it has been implicated as a promoter of gastric cancer growth. In the present study, we demonstrated that the expression level of PCBP2 was higher in human gastric cancer tissues compared to adjacent normal gastric tissues. A high level of PCBP2 was correlated with worse postoperative relapse‐free survival and overall survival rates of gastric cancer patients. Small hairpin RNA‐mediated depletion of PCBP2 dramatically decreased the viability of gastric cancer cells. Cyclin‐dependent kinase 2 (CDK2) was positively regulated by PCBP2 via a direct 3′ UTR binding pathway as determined using a ribonucleoprotein immunoprecipitation assay and a biotin pulldown assay. CDK2 mediated the promoting role of PCBP2. These results suggest that PCBP2 acts as an oncogene in human gastric cancer cells and that functionally depleting PCBP2 could be considered as a potential target for gastric cancer therapy. [ABSTRACT FROM AUTHOR]