Stanniocalcin 2 contributes to aggressiveness and is a prognostic marker for oral squamous cell carcinoma.

Stanniocalcin 2 (STC2), a glycoprotein that regulates calcium and phosphate homeostasis during mineral metabolism, appears to display multiple roles in tumorigenesis and cancer progression. This study aimed to access the prognostic value of STC2 in oral squamous cell carcinoma (OSCC) and its implications in oral tumorigenesis. STC2 expression was examined in 2 independent cohorts of OSCC tissues by immunohistochemistry. A loss-of-function strategy using shRNA targeting STC2 was employed to investigate STC2 in vitro effects on proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition (EMT) and possible activation of signaling pathways. Moreover, STC2 effects were assessed in vivo in a xenograft mouse cancer model. High expression of STC2 was significantly associated with poor disease-specific survival (HR: 2.67, 95% CI: 1.37-5.21, p = 0.001) and high rate of recurrence with a hazard ratio of 2.80 (95% CI: 1.07-5.71, p = 0.03). In vitro downregulation of STC2 expression in OSCC cells attenuated proliferation, migration and invasiveness while increased apoptotic rates. In addition, the STC2 downregulation controlled EMT phenotype of OSCC cells, with regulation on E-cadherin, vimentin, Snail1, Twist and Zeb2. The reactivation of STC2 was observed in the STC2 knockdown cells in the in vivo xenograft model, and no influence on tumor growth was observed. Modulation of STC2 expression levels did not alter consistently the phosphorylation status of CREB, ERK, JNK, p38, p70 S6K, STAT3, STAT5A/B and AKT. Our findings suggest that STC2 overexpression is an independent marker of OSCC outcome and may contribute to tumor progression via regulation of proliferation, survival and invasiveness of OSCC cells.

Maternal polymorphisms in folic acid metabolic genes are associated with nonsyndromic cleft lip and/or palate in the Brazilian population.

BACKGROUND: Polymorphisms in genes that are involved in folic acid metabolism may be important maternal risk factors for the birth of a child with nonsyndromic cleft lip and/or palate (NSCL/P). The aim of this study was to determine the involvement of polymorphic variants in four genes (MTHFR, MTHFD1, MTR, and SLC19A1) that encode proteins related to folic acid metabolism in the women with susceptibility for having a child with NSCL/P. METHODS: DNA samples from 106 mothers of children with NSCL/P (case group) and from 184 mothers of healthy children (control group) were genotyped by polymerase chain reaction associated with restriction fragment length polymorphism (PCR-RFLP). RESULTS: One of 29 polymorphisms was associated with significantly increased maternal risk for NSCL/P. Mothers exhibiting the A variant allele (GA genotype) of the MTHFR rs2274976 polymorphism demonstrated a ~6 times increased risk for having a child with NSCL/P compared to G allele carriers (OR, 5.76; 95% CI, 3.32-9.99, p = 0.000001). Among mothers who did not use vitamins, the OR of NSCL/P was increased to 8.34 (95% CI, 3.75-18.55, p = 0.000001) in the presence of the GA genotype of the MTHFR rs2274976 polymorphism compared to those with the GG genotype. Gene-gene interaction analysis showed that the combination of MTHFR rs2274976, MTHFD1 rs2236225, and SLC19A1 rs1051266 was the best model for prediction of maternal risk for NSCL/P. CONCLUSION: The findings of the present study suggested that genetic variants of folic acid metabolic genes may modulate maternal susceptibility for having an offspring with NSCL/P.