The potential functions of FAM46C in oral squamous cell carcinoma.

Purpose: FAM46C is known as a tumor suppressor in multiple myeloma. However, there are few studies about the expression and function of FAM46C in oral squamous cell carcinoma (OSCC), which is one of the most common oral cancers in the world.

Methods: mRNA and protein expression level were determined by real time PCR and Western blot, respectively. Cell Counting Kit-8 assay and flow cytometry analysis were used to analyze cell proliferation and apoptosis, respectively. Activity of caspase 3 and caspase 9 was determined using biochemical assays.

Results: Our results showed that the OSCC cells overexpressing FAM46C had a relatively slower cell proliferation rate and higher cell apoptosis rate compared with control groups. The results from Western blot showed that the expression levels of cleaved caspase 9 and cleaved caspase 3, which are the active forms of caspase 3 and caspase 9 in FAM46C overexpressed OSCC cells, were higher than in the control cells, while the phosphorylation of ERK1/2 together with its upstream regulators Ras and phosphorylation of MEK1/2 were relatively lower. Additionally, the results also showed that ERK1/2 agonist (EGF) or a caspase 3 inhibitor (Z-DEVD-FMK) inhibited activity of caspase 3 and caspase 9 and cell apoptosis rate. Furthermore, by analyzing FAM46C silencing OSCC cells, we found an increased proliferation rate and a reduced apoptosis rate compared with control cells. And those phenomena could be blocked by U0126, which is an ERK1/2 inhibitor.

Conclusion: Overall, our data suggest that FAM46C probably acts as a tumor suppressor gene in OSCC cells and the working mechanism of FAM46C may be involved in the caspases and ERK1/2 pathway.