Stress induced phosphoprotein 1 promotes tumor growth and metastasis of melanoma via modulating JAK2/STAT3 pathway.

Currently, exploring tumor-promoting or tumor-suppressing factors is a promising approach to find new targets for cancer therapy. In this context, through analysis of GSE datasets (GSE3189 and GSE112509), stress induced phosphoprotein 1 (STIP1) was found to be overexpressed in melanoma tissues compared to benign skin nevi and normal skin tissues, respectively. High expression of STIP1 protein was further confirmed in our melanoma specimens. The survival data of skin cutaneous melanoma in TCGA database indicated that high STIP1 level predicted poor clinical outcomes of patients. Functionally, STIP1 knockdown significantly inhibited cell proliferation, migration and invasion, and induced apoptosis of A2058 cells in vitro. Additionally, STIP1 silencing prominently reduced lung metastasis of melanoma cells in vivo. Whereas, STIP1 overexpression facilitated the growth and metastasis of M14 cells. Intriguingly, STIP1 overexpression markedly increased Janus kinase 2 (JAK2) expression and activated JAK2/signal transducer and activator of transcription 3 (STAT3) pathway in M14 cells, while knockdown of STIP1 blocked JAK2/STAT3 pathway in A2058 cells. Importantly, JAK2 knockdown reversed STIP1-induced melanoma cell proliferation, migration and invasion. Thus, we revealed a novel mechanism underlying STIP1-induced melanoma progression by regulating JAK2/STAT3 pathway. This study might provide a new insight to understand the pathogenesis of melanoma and possibly contributed to development of therapeutic approaches for melanoma.

Correlation of spatio-temporal characteristics of intestinal inflammation with IL-17 in a rat model of hypoganglionosis.

Interleukin 17 expression is increased in children with Hirschsprung disease, which is characterized by intestinal inflammation. This study designed to exploit the characteristics of intestinal inflammation and examine the correlation of interleukin 17 in this process of hypoganglionosis model established by benzalkonium chloride treatment. Colon sections from female rats were treated with benzalkonium chloride to induce hypoganglionosis or with saline alone as a sham control. C-reactive protein and tumor necrosis factor-ɑ were used as markers of inflammation. Expression of C-reactive protein, tumor necrosis factor-ɑ, and interleukin 17 was assessed in colon tissue and blood serum on days 7, 14 and 21 after treatment. The correlation between C-reactive protein, tumor necrosis factor-ɑ, and interleukin 17 expression was estimated using the Spearman's rank-correlation coefficient. C-reactive protein, tumor necrosis factor-ɑ, and interleukin 17 were strongly expressed in submucosa and mucosa layers and serum from treated animals. The expression of C-reactive protein, tumor necrosis factor-ɑ, and interleukin 17 maintained the highest level at Day 21. Only C-reactive protein and tumor necrosis factor-ɑ expression was increased in control animals and only on day 7. Spearman's rank correlation coefficient was significant in C-reactive protein, tumor necrosis factor-ɑ, and interleukin 17 at Day 7, 14 and 21. Concomitant upregulation of C-reactive protein, tumor necrosis factor-ɑ, and interleukin 17 and significant positive correlations between C-reactive protein, tumor necrosis factor-ɑ, and interleukin 17 may imply that interleukin 17 is involved in spatio-temporal inflammation induced by benzalkonium chloride.

MicroRNA-298 represses hepatocellular carcinoma progression by inhibiting CTNND1-mediated Wnt/ß-catenin signaling.

MicroRNAs (miRNAs) are solid factors involved in the initiation and progression of hepatocellular carcinoma (HCC). Recently, miR-298 is recognized as a cancer-associated miRNA in breast, gastric and ovarian cancer. However, the functional role of miR-298 and its underlying mechanism are rarely reported in HCC. Herein, we found that the expression of miR-298 was down-regulated in HCC tissues and cell lines. The in vitro experiments showed that miR-298 overexpression inhibited cell proliferation, migration and invasion, and induced G1 arrest and apoptosis of HCC cells. miR-298 knockdown exerted an opposite effect on these cellular behaviors of HCC cells. Moreover, miR-298 restoration suppressed HCC tumor growth and metastasis in vivo. Additionally, catenin delta 1 (CTNND1) was demonstrated to be a direct target of miR-298 in HCC cells. CTNND1 knockdown led to similar effects with miR-298 overexpression on HCC cell proliferation, cell cycle progression, apoptosis and mobility. CTNND1 restoration reversed miR-298-induced inhibitory effects on HCC cells. Mechanistically, both miR-298 overexpression and CTNND1 knockdown repressed Wnt/ß-catenin signaling and resulted in reduced expression of ß-catenin, WNT11, Cyclin D1 and MMP7 in HCCLM3 cells. While, CTNND1 restoration abolished miR-298-induced inactivation of Wnt/ß-catenin signaling. In conclusion, our findings provide the first evidence that miR-298 suppresses HCC progression at least partially by targeting CTNND1-mediated Wnt/ß-catenin signaling. MiR-298 may be a target for new therapies in HCC patients.

Altered expression of the small guanosine triphosphatase RhoA in human temporal lobe epilepsy.

The small guanosine triphosphatase RhoA has recently been implicated in the pathogenesis of epilepsy in animals. In this study, we investigated the expression of RhoA in human epilepsy. Brain tissue samples from 40 patients with intractable epilepsy and 14 histologically normal temporal lobes from control patients were used to compare RhoA immunoreactivity using immunohistochemistry, immunofluorescent staining, and western blotting. Immunohistochemical staining and western blot analysis showed that RhoA immunoreactivity was increased in the patient group (p < 0.05). Immunofluorescent staining showed that RhoA was mainly expressed on cell membranes and in the cytoplasm. Our findings demonstrate that upregulation of RhoA immunoreactivity occurs in the brains of patients with intractable epilepsy.