ARHGAP15 promotes metastatic colonization in gastric cancer by suppressing RAC1-ROS pathway.

The molecular mechanism of tumor metastasis, especially how metastatic tumor cells colonize in a distant site, remains poorly understood. Here we reported that ARHGAP15, a Rho GTPase activating protein, enhanced gastric cancer (GC) metastatic colonization, which was quite different from its reported role as a tumor suppressor gene in other cancers. It was upregulated in metastatic lymph nodes and significantly associated with a poor prognosis. Ectopic expression of ARHGAP15 promoted metastatic colonization of gastric cancer cells in murine lungs and lymph nodes in vivo or protected cells from oxidative-related death in vitro. However, genetic downregulation of ARHGAP15 had the opposite effect. Mechanistically, ARHGAP15 inactivated RAC1 and then decreased intracellular accumulation of reactive oxygen species (ROS), thus enhancing the antioxidant capacity of colonizing tumor cells under oxidative stress. This phenotype could be phenocopied by inhibition of RAC1 or rescued by the introduction of constitutively active RAC1 into cells. Taken together, these findings suggested a novel role of ARHGAP15 in promoting gastric cancer metastasis by quenching ROS through inhibiting RAC1 and its potential value for prognosis estimation and targeted therapy.

[The relationship between polymorphisms of epidermal growth factor gene and silicosis].

OBJECTIVE: To investigate the relationship between epidermal growth factor (EGF) gene polymorphisms at G-61A, R431K, and D784V and susceptibility to silicosis. METHODS: In a case-control study, 116 patients diagnosed with stage I silicosis were included in the case group, and 149 workers without silicosis of the same gender and nationality, exposed to the same nature of dust, and with similar age and cumulative time of dust exposure were included in the control group. Peripheral venous blood was collected, DNA was extracted by salting out, polymerase chain reaction-restriction fragment length polymorphism was used to identify the genotypes at three polymorphic loci of EGF and the allele frequencies, and their distributions in the case group and control group were analyzed. RESULTS: The genotype frequencies of G-61A GG, GA, and AA in the case group were 50.9%, 34.5%, and 14.7%, respectively, and significant differences were found when comparing the data with those in the control group (35.6%,44.3%, and 20.1%), (χ(2) = 6.283, P = 0.048). The distribution frequencies of allele A in the case group and control group were 31.9%and 42.3%, respectively, and the difference between the two groups was statistically significant (χ2 = 5.554, P = 0.018). The risk of silicosis in workers carrying allele G at G-61A was increased by 1.564 times (OR = 1.564, 95%CI: 1.092∼2.024). The genotype frequencies of D784V AA, AT, and TT in the case group were 58.6%, 34.5%, and 6.9%, respectively, versus 65.1%, 31.5%, and 3.4% in the control group, and the differences between the two groups were not statistically significant (χ(2) = 2.278, P = 0.320). The genotype frequencies of R431K GG, GA, and AA in the case group were 56.9%, 39.7%, and 3.4%, respectively, versus 55.0%, 39.6%, and 5.4% in the control group, and the differences between the two groups were not statistically significant (χ(2) = 0.572, P = 0.751). CONCLUSION: The EGF gene polymorphism at G-61A is associated with susceptibility to silicosis, and the risk of silicosis in dust-exposed workers carrying GG genotype is relatively high. No relationship between EGF gene polymorphisms at D784V and R431K and silicosis is found.

Mechanical properties and acoustic emission characteristics of deep hard coal after segmented high-temperature treatment.

Based on engineering background that local heating of coal seam is uneven due to underground coal gasification, coal-bed gas exploitation via heat injection, spontaneous combustion of coal seam, etc., segmented heating coal sample was used to simulate coal seam under uneven heating condition, and experimental study on mechanical behaviors of coal sample after segmented heat treatment at high temperatures was conducted. Test results show that temperature at 100 °C ~ 400 °C did not reach ignition temperature of deep hard coal for the experiment and was not enough to change main ingredients of coal sample, which less affected compression strength, elastic modulus, acoustic emission behavior of coal sample. Although compaction stage-elastic stage-plastic stage-broken stage appeared in compression stress-strain curve of coal sample, height increase led to decrease of compression strength, elastic modulus of coal sample, cumulative amplitude and ringing count for acoustic emission in the form of power function. Meanwhile, it is found that final failure modes of coal sample after segmented heat were mainly shear failure and separation failure and friction mixed failure was secondary. In addition, influence of heating temperature at 100 °C ~ 400 °C on failure modes of coal sample was small. However, height increase in the heating section of coal sample made shear failure surface gradually move to the heating section and separation failure surface moved with the change of contact surface position between heating section and non-heating section. Furthermore, the integral failure degree of coal sample was more serious. Finally, based on variation behaviors of acoustic emission parameter for coal sample after segmented heating, inversion formula on acoustic emission parameter for strength of coal sample was discussed and verified via experimental result of coal sample with different segmented heat height after heating treatment at 200 °C.