Long noncoding RNA POU6F2-AS2 contributes to the aggressiveness of nonsmall-cell lung cancer via microRNA-125b-5p-mediated E2F3 upregulation.

The role of the majority of long noncoding RNAs (lncRNAs) in the progression of nonsmall-cell lung cancer (NSCLC) remains elusive, despite their potential value, thus warranting in-depth studies. For example, detailed functions of the lncRNA POU6F2 antisense RNA 2 (POU6F2-AS2) in NSCLC are unknown. Herein, we investigated the expression status of POU6F2-AS2 in NSCLC. Furthermore, we systematically delineated the biological roles of POU6F2-AS2 in NSCLC alongside its downstream molecular events. We measured the expression levels of POU6F2-AS2 using quantitative real-time polymerase chain reaction and performed a series of functional experiments to address its regulatory effects in NSCLC cells. Using bioinformatic platforms, RNA immunoprecipitation, luciferase reporter assays, and rescue experiments, we investigated the potential mechanisms of POU6F2-AS2 in NSCLC. Subsequently, we confirmed the remarkable overexpression of POU6F2-AS2 in NSCLC using The Cancer Genome Atlas database and our own cohort. Functionally, inhibiting POU6F2-AS2 decreased NSCLC cell proliferation, colony formation, and motility, whereas POU6F2-AS2 overexpression exhibited contrasting effects. Mechanistically, POU6F2-AS2 acts as an endogenous decoy for microRNA-125b-5p (miR-125b-5p) in NSCLC that causes the overexpression of the E2F transcription factor 3 (E2F3). Moreover, suppressing miR-125b-5p or increasing E2F3 expression levels sufficiently recovered the anticarcinostatic activities in NSCLC induced by POU6F2-AS2 silencing. Thus, POU6F2-AS2 aggravates the oncogenicity of NSCLC by targeting the miR-125b-5p/E2F3 axis. Our findings suggest that POU6F2-AS2 is a novel therapeutic target for NSCLC.

MicroRNA-598 inhibits the proliferation and invasion of non-small cell lung cancer cells by directly targeting ZEB2.

[This retracts the article DOI: 10.3892/etm.2018.6825.].

MicroRNA-598 inhibits the proliferation and invasion of non-small cell lung cancer cells by directly targeting ZEB2.

An increasing number of studies have observed that microRNAs (miRNAs) are abnormally expressed in non-small cell lung cancer (NSCLC), and that their aberrant expression links with the progression and development of NSCLC. Therefore, it is necessary to full elucidate the specific roles of miRNAs in NSCLC, as this may facilitate the identification of novel therapeutic targets. In the present study, it was observed that miRNA-598 (miR-598) expression was significantly downregulated in NSCLC tissues and cell lines. Decreased miR-598 was negatively correlated with TNM stage and lymph node metastasis in NSCLC patients. In addition, ectopic expression of miR-598 reduced NSCLC cell proliferation and invasion in vitro. The zinc finger E-box-binding homeobox 2 (ZEB2) was validated as a direct target of miR-598 in NSCLC cells. ZEB2 was upregulated in NSCLC tissues and the upregulation of ZEB2 was inversely correlated with the miR-598 level. The results revealed that restored ZEB2 expression abrogated the inhibitory effects of miR-598 overexpression in NSCLC cells. In conclusion, the results of the present study revealed that miR-598 may inhibit the progression of NSCLC by directly targeting ZEB2, which suggests that this miRNA may be identified as a potential novel prognostic biomarker and therapeutic target for patients with NSCLC.

MicroRNA-570 promotes lung carcinoma proliferation through targeting tumor suppressor KLF9.

Increasing studies have shown that MicroRNAs (miRNAs) play critical roles in the progression of lung carcinoma. In the present study, the expression and functions of miR-570 were investigated. We found that miR-570 was significantly up-regulated in lung cancer tissues, compared with adjacent non-cancerous tissues. In vitro studies further showed that miR-570 mimics could promote, while its antisense oligos inhibit cell proliferation and invasion. At the molecular level, krüppel-like factor 9 (KLF9), a tumor suppressor gene, was identified as a potential target of miR-570 in lung cancer cells. Indeed, miR-570 could negatively regulate protein levels of KLF9 through targeting its 3'-untranslated region. Taken together, our results suggest a previously unknown miR-570/KLF9 molecular network controlling lung carcinoma progression.

Silencing of Rac3 inhibits proliferation and induces apoptosis of human lung cancer cells.

BACKGROUND: Rac3, a member of the Rac family of small guanosine triphosphatases (GTPases), regulates a variety of cell functions, including the organization of the cytoskeleton, cell migration, and invasion. Overexpression of Rac3 has been reported in several human cancers. However, the role of Rac3 in lung cancer (LC) has not been determined in detail. The purpose of this study was to investigate the effect of silencing of Rac3 expression in human LC cells and the consequences for cell survival. MATERIALS AND METHODS: Lentivirus small hairpin RNA (shRNA) interference techniques were utilized to knock down the Rac3 gene. Gene and protein expression was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. LC cell apoptosis was examined by annexin V-APC /propidium iodide staining. RESULTS: Efficient silencing of Rac3 strongly inhibited A549 cell proliferation and colony formation ability, and significantly decreased tumor growth. Moreover, flow cytometry analysis showed that knockdown of Rac3 led to G2/M phase cell cycle arrest as well as an excess accumulation of cells in the G1 and S phase. CONCLUSIONS: Thus, functional analysis using shRNAs revealed a critical role for Rac3 in the tumor growth of LC cells. shRNA silencing of Rac3 could provide an effective strategy to treat LC.

[Clinical experience of the treatment of solitary pulmonary nodules with Da Vinci surgical system].

BACKGROUND: A solitary pulmonary nodule (SPN) is defined as a round intraparenchimal lung lesion less than 3 cm in size, not associated with atelectasis or adenopathy. The aim of this study is to learn clinical experience of the treatment of SPN with Da Vinci Surgical System. METHODS: A total of 9 patients with solitary pulmonary nodules (SPN) less than 3 cm in diameter was treated with Da Vinci Surgical System (Intuitive Surgical, California) in thoracic surgery department from General Hospital of Shenyang Militrary Region from November 2011 to March 2014. This group of patients included 3 males and 6 females, and the mean age was 51±9.9 yr (range: 41-74 yr). Most of the patients were no obvious clinical symptoms (7 cases were found by physical examination, others were with cough and expectoration). Their median medical history was 12 mo (range: 4 d-3 yr). All the lesions of patients were peripheral pulmonary nodules and the mean diameter of those was (1.4±0.6) cm(range: 0.8-2.8 cm). Wedge-shaped resection or lobectomy was performed depending on the result of rapid pathology and systemic lymph node dissection was done for malignant leision. We used general anesthesis with double lumens trachea cannula. We set the patients in lateral decubitus position with jackknife. The patient cart enter from top of the patient. The position of trocars would be set according to the position of lesion. A 12 mm incision was positioned at the 8th intercostal space in the posterior axillary line as vision port, and two 8 mm incisions were positioned at the 5th intercostal space between the anterior axillary line and midclavicular line, and the 8th infrascapular line as robotic instrument ports about 10 cm apart from the vision port. One additional auxiliary small incision for instrument without retracting ribs was set at the 7th intercostal space in the middle axillary line. RESULTS: There were 4 benign leisions and 5 malignancies identified. Wedge-shaped resection was performed for 4 patients, lobectomy with systemic lymph node dissection for 3 patients (including 2 right middle lobectomies and 1 left upper lobectomy) and wedge-shaped resection with systemic lymph node dissection for 2 patients of poor lung function. All of the 9 cases were completed with total robotic procedure without conversion. The pathological results included 3 inflammatory pseudotumors, 1 hamartoma, 5 adenocarcinomas. All of the 29 patients were hospital discharged smoothly. The patients were followed up for 0.1-18.5 mo (median 11 mo) without recurrence or metastasis. CONCLUSIONS: The SPN patients should be given active surgical treatments to improve the diagnose rate as well as the cure rate of early non-small cell lung cancer. Since da Vinci Surgical System is a safe and minimally invasive treatment for SPN, it has higher value to the diagnosis and treatment of SPN.

[A comparative study of Da Vinci robot system with video-assisted thoracoscopy in the surgical treatment of mediastinal lesions].

BACKGROUND: In recent years, Da Vinci robot system applied in the treatment of intrathoracic surgery mediastinal diseases become more mature. The aim of this study is to summarize the clinical data about mediastinal lesions of General Hospital of Shenyang Military Region in the past 4 years, then to analyze the treatment effect and promising applications of da Vinci robot system in the surgical treatment of mediastinal lesions. METHODS: 203 cases of mediastinal lesions were collected from General Hospital of Shenyang Military Region between 2010 and 2013. These patients were divided into two groups da Vinci and video-assisted thoracoscopic surgery (VATS) according to the selection of the treatments. The time in surgery, intraoperative blood loss, postoperative drainage amount within three days after surgery, the period of bearing drainage tubes, hospital stays and hospitalization expense were then compared. RESULTS: All patients were successfully operated, the postoperative recovery is good and there is no perioperative death. The different of the time in surgery between two groups is Robots group 82 (20-320) min and thoracoscopic group 89 (35-360) min (P>0.05). The intraoperative blood loss between two groups is robot group 10 (1-100) mL and thoracoscopic group 50 (3-1,500) mL. The postoperative drainage amount within three days after surgery between two groups is robot group 215 (0-2,220) mL and thoracoscopic group 350 (50-1,810) mL. The period of bearing drainage tubes after surgery between two groups is robot group 3 (0-10) d and thoracoscopic group: 5 (1-18) d. The difference of hospital stays between two groups is robot group 7 (2-15) d and thoracoscopic group 9 (2-50) d. The hospitalization expense between two groups is robot group (18,983.6±4,461.2) RMB and thoracoscopic group (9,351.9±2,076.3) RMB (All P<0.001). CONCLUSIONS: The da Vinci robot system is safe and efficient in the treatment of mediastinal lesions compared with video-assisted thoracoscopic approach, even though its expense is higher.

[Video-assisted thoracic surgery: clinical experience among 1264 patients].

OBJECTIVE: To summarize the clinical experience in video-assisted thoracic surgery (VATS). METHODS: From December 1993 to December 2005 1264 patients, 894 males and 370 females, aged 38.9 +/- 12.0, underwent VATS, including bullectomy in 622 cases, resection of mediastinal tumor or cyst in 119 cases, resection of esophageal diseases in 107 cases, lobectomy or wedge-shaped lung resection in 215 cases, lung volume reduction surgery (LVRS) in 17 cases, treatment of thoracic injury in 28 cases, treatment of other thoracic diseases in 72 cases, and biopsy in 84 cases. For the resection of esophageal carcinoma VATS was conducted via the right approach, the esophagus was dissociated, the lymph nodes were resected, upper-abdominal incision was made, the stomach was dissociated and drawn up to the neck region, a cervical incision was made to anastomose the stomach and the residue of esophagus. RESULTS: Operation was completed by VATS successfully in 1230 patients, and 34 cases were converted to traditional thoracotomy because of thoracic adhesion or to radically treat the malignant tumors. Major complications occurred in 45 cases (3.56%), including air-leak lasting more than 7 days in 30 cases, post-operative bleeding in 4 cases (3 of which received VATS once more for hemostasis and the other underwent thoracotomy), hydrothorax or pneumothorax in 3 cases that underwent water-closed drainage, esophageal mucous rupture in 4 cases with achalasia and one case with leiomyoma, all of which underwent repair immediately, infection of pleural cavity in one case after the resection of esophageal diverticulum, and pneumonia in one case after LVRS. One patient with spontaneous pneumothorax and respiratory failure died 5 days after the bullectomy. Spontaneous pneumothorax occurred in 10 patients 2 months to 2 years after VATS 3 of which underwent bullectomy and pleurodesis by VATS once more. CONCLUSION: Spontaneous pneumothorax and some benign thoracic diseases are the major indications of VATS; however, great care should be expended to decide to treat malignant diseases by VATS. It is very important to train the surgeons who are to practice VATS. The practice of VATS should be individualized.

[The role of Smad4 and MAPK proteins in signal transduction pathway in non-small cell lung cancer].

OBJECTIVE: To investigate the expression of Smad4 in non-small cell lung cancer (NSCLC), its correlation with MAPK (mitogen activated protein kinase) and their clinical significance in NSCLC. METHODS: Western blotting and RT-PCR were employed to test 42 resected lung cancers and normal lung tissues for the expression of Smad4. Imunohistochemistry was used to detect Smad4 and subtribes of MAPK in 71 paraffin samples. RESULTS: The level of protein and mRNA expression of Smad4 in lung cancer tissues were 0.2092 +/- 0.1308 and 0.3986 +/- 0. 1982, respectively, lower than those in normal tissues (0.7852 +/- 0.4386 and 1.1206 +/- 0.6772, P < 0.05). The expression of p38, ERK1 and Smad4 was associated with TNM staging (P = 0.000, 0.000 and 0.005, respectively) and JNK1 with tumor location (P = 0.028) and staging (P = 0.000). There was a correlation between p38 and Smad4 (P = 0.000). The expression of Smad4 (P = 0.0001), p38 (P = 0.0000) and JNK1 (P = 0.0208), tumor differentiation (P = 0.0059) and staging (P = 0.0000) were significantly correlated with prognosis of NSCLC by univariate analysis. Smad4 (P = 0.019), p38 (P = 0.044), tumor differentiation (P = 0.003), and staging (P = 0.020) were correlated with prognosis tested by multivariable analysis. Taking p38 and Smad4 together, we found that the negative expression of p38 and positive expression of Smad4 were associated with a better prognosis of NSCLC (P = 0.000). CONCLUSION: Smad4 could be of importance for the initiation and development of NSCLC. There is a significant correlation between main proteins of TGF-beta/smad4 and those of ras-MAPK signal transduction pathways. The expression of Smad4 is inhibited by p38. Smad4, as well as p38, tumor differentiation and staging can be used as prognostic factors of NSCLC.

[Tracheo-bronchoplasty and/or cardiovascular reconstruction in the treatment of centrally located lung cancer].

BACKGROUND: To explore the feasibility of extended resection in selective patients with centrally located lung cancer. METHODS: From January, 1987 to December, 2001, lobectomy or pneumonectomy combined with extended resection of trachea, bronchus, heart or great vessels were carried out in 134 patients with centrally located lung cancer. The operations included bronchoplastic procedures in 80 cases, extended resection and reconstruction of left atrium and/or great vessels in 54 cases (32 cases with contemporary bronchoplasty). RESULTS: Operative death occurred in one case. Postoperative complications happened in 16 cases (11.9%). One hundred and seventeen cases (94.4%) were followed up. The 1-, 3-, 5-year survival rate was 84.7% (61/72), 56.7% (34/60) and 45.7% (21/46) respectively, while of those combined with tracheo bronchoplasty and/or cardiovascular reconstruction, the 1-, 3-, 5-year survival rate was 69.2% (36/52), 46.8% (22/47) and 22.2% (8/36) respectively. (P < 0.05), while expression of KAI1 mRNA did not relate to mutant P53 protein expression (P > 0.05). CONCLUSIONS: Extended resection combined with tracheo-bronchoplasty and/or cardiovascular reconstruction is feasible for selected patients with centrally located lung cancer and could improve the survival and life quality of patients.