MiR-596 down regulates SOX4 expression and is a potential novel biomarker for gastric cancer.

Background: Gastric cancer (GC) is one of the most commonly diagnosed malignancies of the human digestive tract, and currently there is a dearth of effective biomarkers for this disease.

Methods: MiR-598 expression levels were analyzed by the cancer genome atlas (TCGA database) mining and verified in GC patient plasma using real-time reverse transcription polymerase chain reaction (RT-PCR) assay. We used the GEPIA and UALCAN databases and immunohistochemistry (IHC) to analyze SOX4 expression. The MTT assay assessed MNK28 and SGC7901 cell proliferation after transfection with miR-596 plasmids. The analytical tools, Functional Enrichment Analysis Tool (FunRich), Database of Immune Cell Expression (DICE) and Tumor IMmune Estimation Resource (TIMER) were used to analyze correlations between SOX4 and immune responses. Furthermore, a Kaplan Meier plotter database explored correlations between miR-596, SOX4 and overall patient survival.

Results: Data from TCGA and RT-PCR indicated that miR-598 was lowly expressed in GC patients. The miRWalk database showed that SOX4 was the target genes of miR-596 and also revealed that miR-596 bound directly to SOX4. MiR-596 over-expression further depressed GC cell proliferation. In addition, the FunRich database showed that SOX4 was involved in immune responses, and was further shown to be differentially expressed in CD4+ T cells by DICE. Specifically, TIMER indicated that high expression of SOX4 was negatively correlated with infiltrating CD4+ T cells in stomach adenocarcinoma (STAD). Moreover, high expression of miR-596 and low expression of SOX4 prolonged the overall survival (OS) of GC patients.

Conclusions: Our study reveals a crucial role for miR-596 in tumor-associated immune infiltration and predicting prognoses in GC patients.