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Objective: Oncogenes have been shown to be drivers of non-small cell lung cancer (NSCLC), yet the tumor suppressing genes involved in lung carcinogenesis remain to be systematically investigated. This study aimed to identify tumor suppressing ubiquitin pathway genes (UPGs) that were critical to lung tumorigenesis. Methods: The 696 UPGs were silenced by an siRNA screening in NSCLC cells; the potential tumor suppressing UPGs were analyzed, and their clinical significance was investigated. Results: We reported that silencing of 11 UPGs resulted in enhanced proliferation of NSCLC cells, and four UPGs (UBL3, TRIM22, UBE2G2, and MARCH1) were significantly downregulated in tumor samples compared to that in normal lung tissues and their expression levels were positively associated with overall survival (OS) of NSCLC patients. Among these genes, UBL3 was the most significant one. UBL3 expression was decreased in tumor samples compared to that in paired normal lung tissues in 59/86 (68.6%) NSCLCs, was correlated with TNM stage and sex of NSCLC patients, and was significantly higher in non-smoking patients than in smoking patients. Silencing UBL3 accelerated cell proliferation and ectopic expression of UBL3 suppressed NSCLC in vitro and in vivo. Conclusions: These results showed that UBL3 represented a tumor suppressor in NSCLC and may have potential for use in therapeutics and for the prediction of clinical outcome of patients.

OBJECTIVE To explore the application of blocking the unilateral main pulmonary artery (MPA) in pulmonary lobectomy (PL) for patients with stage II and III lung cancer, and to retrospectively analyze the methods of surgery for blocking the unilateral main pulmonary artery, perioperative indications, intraoperative concerns and postoperative cardio-pulmonary complications. METHODS During a period from January 2006 to January 2008, intra-pericardial, or extra-pericardial separation and blockade of the le t or right MPA followed by completion of various PLs were conducted for 30 lung cancer patients in stage-II to III with ill-defi ned anatomic structure of the pulmonary hilum and difficult pulmonary angiodiastasis. RESULTS In the 30 patients, 5 were diagnosed as stage-IIb, 11 stage-IIIa, and 14 stage-IIIb. During the surgery, giant tumors at the superior pulmonary lobe, with a diameter of over 10 cm, were seen in 13 cases, in which tumor invasion in the extra pericardiac pulmonary artery was found in 5 cases. Hilar lymphadenectasis with severe tumor adhesion to pulmonary blood vessel could be seen in 20 cases and partial tumorous invasion in the pericardium in 7. In most of the cases, adhesions existed around the tumor, aorta, superior vena, and azygous vein. Invasion of the laryngeal and vagus nerves on the left side was found in 3 cases. Of the 30 patients, simple PL was conducted in 12, and sleeve lobectomy combined with a pulmonary arterioplasty in 18 cases. With a blockade of unilateral MPA, no intraoperative hemorrhea of pulmonary blood vessels occurred during surgery, when there was a clear surgical field of vision. Both PL and lymphadenectomy were smoothly completed in the 30 patients. The healthy pulmonary lobes with normal function were kept and total pneumonectomy was avoided. The time of blocking the pulmonary artery ranged from 10 to 30 min, and intraoperative blood loss was from 200 to 300 ml. Postoperative complicated acute pulmonary edema occurred in 5 patients and tachycardia in 7 cases. Nevertheless, all patients recovered and let the hospital after treatment. No severe cardiopulmonary complications were found in all patients of the group. CONCLUSION Blocking the unilateral MPA is effective to decrease the risk of intraoperative hemorrhea in the PL. It can shorten the time of surgery, improve the excision rate of lung cancer, and cut down on the rate of total pneumonectomy.