ETS1 promoted cell growth, metastasis and epithelial-mesenchymal transition process in melanoma by regulating miR-16-mediated SOX4 expression.

Melanoma is a malignant tumor with high metastasis and mortality. Epithelial-mesenchymal transition (EMT) was reported to be involved in the growth and metastasis of melanoma. To investigate these sections further, we showed that E26 transformation specific 1 (ETS1) could regulate growth, metastasis and EMT process of melanoma by regulating microRNA(miR)-16/SRY-related HMG box (SOX) 4 expression. MiR-16, ETS1, SOX4 and nuclear factor κB (NF-κB) expression levels in melanoma cells were examined using qPCR. ETS1, SOX4, EMT-related proteins and NF-κB signaling pathway-related proteins were examined using western blot. Cell counting kit-8 assay, transwell assay were applied to evaluate the cell proliferation, migration and invasion of melanoma cells, respectively. Besides, a dual-luciferase reporter assay was employed to verify the binding relationship between ETS1 and miR-16, miR-16 and SOX4, miR-16 and NF-κB1. We showed that ETS1 and SOX4 were upregulated in melanoma cells, while miR-16 was downregulated. MiR-16 overexpression suppressed growth, metastasis and EMT process of melanoma. We found ETS1 could bind to the promoter region of miR-16 and inhibited its transcription. ETS1 silence could inhibit growth, metastasis and EMT process of melanoma, and inhibition of miR-16 could reverse the effects. Besides, miR-16 is directly bound to SOX4 and downregulated its expression. Rescued experiments confirmed that SOX4 overexpression abolished the inhibition effect of miR-16 mimics on growth, metastasis and EMT process of melanoma. Finally, NF-κB1 as the target of miR-16 mediated downstream biological responses. ETS1 activated NF-κB signaling pathway through miR-16 via targeting SOX4, thus promoting growth, metastasis and EMT of melanoma.

One-stage surgical management for tuberculosis of the upper cervical spine by posterior debridement, short-segment fusion, and posterior instrumentation in children.

PURPOSE: To evaluate the clinical study efficacy and feasibility of 11 children with tuberculosis of the upper cervical spine treated by one-stage posterior debridement, short-segment fusion, and posterior instrumentation. METHODS: Eleven children who suffered from tuberculosis of the upper cervical spine were admitted to our hospital between June 2005 and December 2010. All of them were treated by one-stage posterior debridement, short-segment fusion, and posterior instrumentation. Then, the clinical efficacy was evaluated using statistical analysis based on the materials about the visual analogue scale (VAS) scores of pain, JOA scores of nerve function and erythrocyte sedimentation rate (ESR), which were collected at certain time. RESULTS: The average follow-up period was 28.1 ± 10.5 months (13-42 months). In the 11 cases, no postoperative complications related to instrumentation occurred and neurologic function was improved in various degrees. The average pretreatment ESR was 58.4 ± 4.9 mm/h (53-69 mm/h), which got normal (8.9 ± 6.5 mm/h) within 3 months in all patients. The average preoperative VAS was 7.4 ± 2.2, which decreased to 1.6 ± 1.8 postoperatively. Mean preoperative JOA was 11.2 ± 3.8, and the JOA at the last visit was 16.3 ± 1.0. All patients got bony fusion within 3-8 months after surgery. CONCLUSIONS: One-stage posterior debridement, short-segment fusion, and posterior instrumentation can be an effective treatment method for the treatment of tuberculosis of the upper cervical spine in children.