ABSTRACT
Ubiquitin specific peptidase 49 (USP49) has been reported as a tumor suppressor in several tumors, but its function and molecular mechanism in non-small cell lung cancer (NSCLC) are still unknown. In this study, USP49 was found downregulated in NSCLC primary tissues and cell lines, and high USP49 predicted a positive index for the overall survival of NSCLC patients. Overexpression of USP49 downregulated the expression levels of Cyclin D1, and upregulated p53 expression. Further flow cytometry analysis showed that overexpressed USP49 induced cell cycle arrest at G0/G1 phase. As a result, overexpression of USP49 significantly inhibited cell growth of NSCLC cells. In mechanism, overexpression of USP49 inhibited PI3K/AKT signaling, but knockdown of USP49 enhanced this signaling. Further studies indicated that USP49 deubiquitinated PTEN and stabilized PTEN protein, which suggested that USP49 inhibited PI3K/AKT signaling by stabilizing PTEN in NSCLC cells. In conclusion, we demonstrated that USP49 was functional in NSCLC cells, and inhibited NSCLC cell growth by suppressing PI3K/AKT signaling, suggesting that USP49 could be as a novel target for NSCLC therapy.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Gene Expression Regulation, Neoplastic , Lung Neoplasms/genetics , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Ubiquitin Thiolesterase/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Cell Cycle Checkpoints/genetics , Cell Line, Tumor , Cell Proliferation , Cyclin D1/genetics , Cyclin D1/metabolism , HEK293 Cells , Humans , Lung/metabolism , Lung/pathology , Lung Neoplasms/metabolism , Lung Neoplasms/mortality , Lung Neoplasms/pathology , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Resting Phase, Cell Cycle , Signal Transduction , Survival Analysis , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Ubiquitin Thiolesterase/antagonists & inhibitors , Ubiquitin Thiolesterase/metabolismSubject(s)
Amino Acids/therapeutic use , Blood Coagulation Disorders/drug therapy , Hemorrhage/drug therapy , Vitamin B 6/therapeutic use , Wounds and Injuries/drug therapy , Adult , Aged , Blood Coagulation Disorders/complications , Drug Combinations , Female , Humans , Male , Middle Aged , Vitamin B 6/administration & dosage , Wounds and Injuries/complications , Young AdultABSTRACT
OBJECTIVE: To investigate the characteristics of the confined space accident and its medical rescue strategy. METHODS: Thirty-six patients with emergency rescue in the five confined space accident during June 2009 to July 2012 were retrospectively analyzed. RESULTS: Twenty-nine people were caught in four confined space accidents caused by building collapse and 7 people were caught in one confined space accident caused by a tower of babel blast furnace damage which caused severe gas and hydrogen sulfide poisoning. For the 36 wounded, the shortest rescue time was 1.5 hours and the longest was 10.5 hours. Fourteen people were killed (mortality rate 38.89%). Characteristics of the confined space accident: the wounded activity environment was very harsh, the wounded were restricted particularly, the wounded injuries were diverse, the psychological depression was very common. The confined space environment and the complexity of wounded disease determined its medical rescue specificity and were very different from the usual trauma emergency. CONCLUSIONS: Confined space accident caused very painful casualties. The key reason is that the relevant personnel failed to clearly recognize the potential risks in the confined space or nearby, making the confined space into another "quiet killer". This problem needs to be paid highly attention.
