The minichromosome maintenance complex 3 (MCM3) is essential for the regulation of DNA replication and cell cycle progression. However, the expression and prognostic values of MCM3 in cervical cancer (CC) have not been well-studied. Herein, we investigated the expression patterns and survival data of MCM3 in cervical cancer patients from the ONCOMINE, GEPIA, Human Protein Atlas, UALCAN, Kaplan-Meier Plotter, and LinkedOmics databases. The expression level of MCM3 is negatively correlated with advanced tumor stage and metastatic status. Specifically, MCM3 is significantly differentially expressed between patients in stage 1 and stage 3 cervical cancer with
p
value 0.0138. Similarly, the
p
values between stage 1 and stage 4 cervical cancer, between stage 2 and stage 3, and between stage 2 and stage 4 are 0.00089, 0.0244, and 0.00197, respectively. Not only that, cervical cancer patients with high mRNA expression of MCM3 may indicate longer overall survival but indicate shorter relapse-free survival. PRIM2 and MCM6 are positively correlated genes of MCM3. Bioinformatics analysis revealed that MCM3 might be considered a biological indicator for prognostic evaluation of cervical cancer. However, it is currently limited to bioinformatics analysis, and more clinical tissue specimens and cell experiments are needed to further explore the role of MCM3 in the occurrence and progression of cervical cancer.
OBJECTIVE
As a ligand of NKp30, B7 homolog 6 (B7-H6) is involved in the immune regulation of various tumors. The aim of this study was to clarify the effect of B7-H6 expressed in HeLa cells on NK cell killing function.
METHODS
The expression of B7H6 was changed in HeLa cells using short hairpin RNA. Furthermore the effect of B7-H6 on the killing function of NK cell was analyzed after cell co-culture. Flow cytometry was used to detect NKp30 expression, degranulation function, perforin (PFP) and Granzyme B (GZMB) secretion function of NK cells. Enzyme-linked immunosorbent assay (ELISA) was used to detect interferon-γ (INF-γ) production function. The cytotoxicity of NK-92 cells was determined using the CytoTox 96 Non-Radio active Cytotoxicity Assay. Western blotting (WB) detection was used to detect the ERK phosphorylation level in NK cells.
RESULTS
When NK-92 cells co-cultivated with HeLa cells with different expression levels of B7-H6, the expression of NKp30, NK-92 cell killing rate, PFP and INF-γ production, and degranulation function were correspondingly changed in NK cells, but there is no effcet on GZMB production. After cell co-culture, ERK phosphorylation level in NK cells was increased gradually with the up-regulation of B7-H6 expression.
CONCLUSIONS
B7-H6 can enhance the killing function of NK cells to HeLa cells by activating the NKp30 downstream ERK signaling pathway.
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