RUNX1-induced upregulation of PTGS2 enhances cell growth, migration and invasion in colorectal cancer cells.

Colorectal cancer (CRC) arises via the progressive accumulation of dysregulation in key genes including oncogenes and tumor-suppressor genes. Prostaglandin-endoperoxide synthase 2 (PTGS2, also called COX2) acts as an oncogenic driver in CRC. Here, we explored the upstream transcription factors (TFs) responsible for elevating PTGS2 expression in CRC cells. The results showed that PTGS2 silencing repressed cell growth, migration and invasion in HCT116 and SW480 CRC cells. The two fragments (499-981 bp) and (1053-1434 bp) were confirmed as the core TF binding profiles of the PTGS2 promoter. PTGS2 expression positively correlated with RUNX1 level in colon adenocarcinoma (COAD) samples using the TCGA-COAD dataset. Furthermore, RUNX1 acted as a positive regulator of PTGS2 expression by promoting transcriptional activation of the PTGS2 promoter via the 1086-1096 bp binding motif. In conclusion, our study demonstrates that PTGS2 upregulation induced by the TF RUNX1 promotes CRC cell growth, migration and invasion, providing an increased rationale for the use of PTGS2 inhibitors in CRC prevention and treatment.

Identifying the dose response relationship between seminal metal at low levels and semen quality using restricted cubic spline function.

Environmental exposure to metals, including essential and nonessential elements, may be related to semen quality. Our goal was to explore the continuous relationship between seminal metals and sperm parameters. A restricted cubic spline (RCS) was applied to automatic selection criteria to ascertain the optimal smoothing degree. We recruited 841 male volunteers from Henan Province, China. Eighteen seminal metals, namely Al, Cr, Mn, Cu, Zn, Se, As, Ni, Cd, Pb, Co, V, Rb, Ag, Ba, TI, Fe, and Li, and 21 semen parameters were detected. Seminal malondialdehyde (MDA) was also detected to express oxidative stress. We revealed a non-linear relationship of the vanadium and chromium exposure to semen parameters. There were inverse 'U' shapes found between seminal Cr and sperm concentrations, total sperm count, and semen quality. The best semen quality was observed when the seminal Cr concentration was 5.05 ppb, and an increase or decrease in chromium concentration led to decreased semen quality. The V concentration was associated with reduced sperm concentration, total sperm count, normal morphology, and progressive motility at high doses (V > 0.58 ppb). Seminal MDA had a strong adverse association with sperm motility parameters, such as curve line velocity (VCL) (P < 0.001), straight line velocity (VSL) (P = 0.004), velocity of average path (VAP) (P < 0.001), and lateral head movement (ALH) (P = 0.001), whereas it was adversely associated with seminal Zn (ß [95% confidence interval (CI)], -0.28(-0.41-0.16), P < 0.001) after adjusting for confounding factors. Our findings represent the curves of the dose-response relationship between seminal Cr, seminal V, and semen quality, in which seminal MDA was a good indicator of sperm movement. These models provide new insight into the dose-relationship between metal exposure and semen quality, and further investigation is needed to validate this.