Knockdown of metadherin inhibits cell proliferation and migration in colorectal cancer.

Metadherin (MTDH) is a multifunctional oncogene involved in tumor cell migration and metastasis through regulating a number of oncogenic signaling pathways in various human malignancies. Previous studies have demonstrated that MTDH is overexpressed in human colorectal cancer (CRC) and associated with cancer progression and a poor prognosis. However, the underlying mechanisms remain largely unknown. The present study investigated the expression and role of MTDH in CRC cells as well as the underlying mechanism of this. Western blot analysis and quantitative polymerase chain reaction were conducted to determine protein and mRNA expression of MTDH in three human CRC cell lines. A short hairpin RNA (shRNA) targeting MTDH was introduced into CRC HCT116 cells to stably inhibit MTDH expression. A Cell Counting Kit­8 assay, colony formation assay, Transwell assay and flow cytometry were used to investigate the effect of MTDH­knockdown on cell proliferation, migration, apoptosis and cell cycle arrest. Western blotting was performed to examine the protein expression levels of cell growth­ and apoptosis­associated genes. The results demonstrated that MTDH was commonly expressed in CRC cell lines. MTDH silencing significantly suppressed cell growth, colony forming ability and migration while inducing the apoptosis of HCT116 cells. In addition, MTDH depletion induced S phase cell cycle arrest in HCT116 cells. Mechanistically, knockdown of MTDH markedly downregulated the expression of phosphorylated protein kinase B, c­Myc, proliferating cell nuclear antigen and B­cell lymphoma 2 (Bcl­2) protein in HCT116 cells, and the expression of p53 and Bcl­2­associated X protein was significantly increased compared with the negative control shRNA group (P<0.05), suggesting that MTDH may function through the expression of numerous types of apoptosis­associated and signaling channel proteins in CRC cells. Taken together, these data indicated that MTDH may serve as a biomarker and candidate therapeutic target for CRC.

Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in hepatocellular carcinoma cells.

This work aims to study the roles and related mechanisms of six2 in 5-FU sensitivity of hepatocellular carcinoma (HCC) cells. KM-Plotter analysis showed that HCC patients with higher six2 expression levels had shorter overall survival. Six2 expression was higher in clinical HCC tissues than in normal tissues, and was negatively correlated with E-cadherin expression. Additionally, six2 overexpression decreased the sensitivity of HCC cells to 5-Fu, characterized as attenuating 5-FU-induced cell apoptosis and downregulation of cell viability, and promoted HCC cells stemness. Mechanistically, six2 overexpression repressed E-cadherin expression via stimulating promoter methylation of the E-cadherin. And E-cadherin overexpression rescued six2-induced decrease of 5-FU sensitivity and promotion on HCC cells stemness. Therefore, our results suggest that Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in HCC cells.

The pro-inflammatory cytokines, salivary cortisol and alpha-amylase are associated with generalized anxiety disorder (GAD) in patients with asthma.

Generalized anxiety disorder (GAD) is common in patients with asthma. High levels of GAD may lead both to exacerbation of the condition and poor management. However, the physiological mechanisms of GAD in asthma patient is unclear. This study investigated the associations between the diurnal rhythm of sputum cytokines, salivary cortisol, α-amylase and GAD in asthma patients. Patients with co-morbid GAD and asthma showed higher sputum IL-1 AUC, sputum IL-6 AUC and sAA AUC. And there were positive correlations between Hamilton anxiety scale (HAMA) scores and sputum IL-1 AUC concentrations (r=0.37, P=0.002), HAMA scores and sputum IL-6 AUC (r=0.56, P<0.001), HAMA scores and sAA AUC (r=0.75, P<0.001). Also, there were positive correlations between Sputum IL-1 AUC and sAA AUC (r=0.40, P<0.001), between Sputum IL-6 AUC and sAA AUC. Stepwise multiple regression analyses showed the combination of sputum sAA AUC, IL-1 AUC, IL-6 AUC and cortisol AUC was the best predictor of HAMA scores (ΔR2=0.439, F(4,63)=14.086, p<0.001). Therefore, pro-inflammatory cytokines, salivary cortisol and alpha-amylase may all be involved in the occurrence of GAD in asthma patients.