Liver X receptors agonist T0901317 downregulates matrix metalloproteinase-9 expression in non-small-cell lung cancer by repressing nuclear factor-κB.

The liver X receptors (LXRs) is an important component of the nuclear receptor (NR) superfamily. Previous studies have shown that the LXRs possessed antitumor activity in various types of tumor cells. However, the complicated mechanisms underlying the antitumor activity remain largely unexplored. In this study, we incubated A549 cells with the compound T0901317, a specific LXRs agonist, for 24 h. The MTT assay was used to assess cell viability. Transwell assays were used to evaluate cell migration and invasion. The shRNA was utilized for RNA interference. The target gene and protein expression levels were assessed using reverse transcription-PCR and western blot assay. The DNA-binding activity of nuclear factor κB (NF-κB) was examined using electrophoretic mobility shift assays. Luciferase reporter assay was used to detect the binding of NF-κB to the matrix metalloproteinase-9 (MMP-9) promoter. We found that T0901317 inhibited the invasion and migration of A549 cells in a dose-dependent manner. Meanwhile, we further indicated that activation of LXRß, one subtype of LXRs, can downregulate MMP-9 expression. More importantly, activation of LXRß triggered by T0901317 inhibited the invasion and metastasis of A549 cells by repressing NF-κB/MMP-9 signaling pathway. Taken together, our study shows that activation of LXRs triggered by T0901317 inhibits the invasion and metastasis of human non-small-cell lung cancer by repressing the NF-κB/MMP-9 signaling pathway.

Association between BIM deletion polymorphism and clinical outcome of EGFR-mutated NSCLC patient with EGFR-TKI therapy: A meta-analysis.

AIM: BIM deletion polymorphism was deemed to be associated with downregulation of BIM, resulting in a decreased apoptosis induced by epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutation-positive non-small cell lung cancer (NSCLC). However, accumulating evidences concerning the association between BIM deletion polymorphism and efficacy of EGFR-TKI and survival in EGFR-mutation-driven NSCLC patient reported contradictory results. MATERIALS AND METHODS: A meta-analysis was conducted by combing six original eligible studies including 871 NSCLC patients. RESULTS: Our study showed that BIM deletion polymorphism was significantly associated with poor response to EGFR-TKI therapy in mutant EGFRNSCLC patients (P(h) = 0.309, P(z) = 0.001, OR = 0.39, 95% confidence interval (CI) = 0.23-0.67). Disease control rate (DCR) in mutant EGFRNSCLC patient with treatment of EGFR-TKI was significantly decreased in patients with BIM deletion polymorphism comparing to patients harbored BIM wild variant (P(h) = 0.583, P(Z) = 0.007, OR = 0.46, 95%CI = 0.25-0.85). EGFR mutation-derived NSCLC patient carrying BIM deletion polymorphism had a shorter progression-free survival (PFS; P(h) < 0.001, P(z) < 0.001, hazard ratio (HR) = 1.37, 95%CI = 1.09-1.71) and overall survival (OS; P(h) = 0.90, P(z) = 0.003, HR = 1.25, 95%CI = 1.08-1.45), than those harbored BIM wild variant. CONCLUSION: These results suggested that BIM deletion polymorphism might be a cause that contributes to primary EGFR-TKI resistance, and it could be used as a genetic predictor for EGFR-TKI outcome and an independent prognostic factor of EGFR mutation-driven NSCLC patient.

Rs895819 within miR-27a might be involved in development of non small cell lung cancer in the Chinese Han population.

MicroRNA-27a (miR-27a) is deemed to be an oncogene that plays an important role in development of various cancers, and single nucleotide polymorphism (SNP) of miR-27a can influence the maturation or aberrant expression of hsa-miR27a, resulting in increased risk of cancer and poor prognosis for non-small cell lung cancer (NSCLC). This study aimed to assess the effects of rs895819 within miR-27a on susceptibility and prognosis of NSCLC patients in 560 clinical confirmed cases and 568 healthy check-up individuals. Adjusted odds/hazard ratios (ORs/HRs) and 95% confidential intervals (CIs) were calculated to evaluate the association between rs895819 and the risk and prognosis of NSCLC. The results showed that allele A and genotype GG of rs895819 were significantly associated with an increased risk of NSCLC (38.9% vs 30.8%, adjusted OR=1.26, 95%CI=1.23-1.29 for allele G vs A; 18.1% vs 11.7%, adjusted OR=1.67, 95%CI=1.59-1.75 for genotype GG vs AA). Moreover, positive associations were also observed in dominant and recessive models (53.7% vs 49.9%, adjusted OR=1.17, 95%CI=1.13-1.20 for GG/AG vs AA; 18.1% vs 11.7%, adjusted=1.65, 95%CI=1.58-1.73). However, no significant association was found between rs895819 and the prognosis of NSCLC in genotype, dominant and recessive models. These results suggested that miR-27a might be involved in NSCLC carcinogenesis, but not in progression of NSCLC. The allele G, genotype GG and allele G carrier (GG/AG vs AA) of rs895819 might be genetic susceptible factors for NSCLC. Further multi-central, large sample size and well-designed prospective studies as well as functional studies are warranted to verify our findings.

Expression and significance of circulating microRNA-31 in lung cancer patients.

BACKGROUND: The aim of this study was to investigate the expression level of circulating microRNA-31(miRNA-31) in lung cancer patients and its clinical significance. MATERIAL AND METHODS: Real-time fluorescent quantitative PCR was utilized to detect the circulating miRNA-31 expression levels in 300 lung cancer patients and 300 health control subjects. The ROC curve was drawn to evaluate the diagnostic value of the circulating miRNA-31 expression levels in lung cancer. The 300 lung cancer patients were divided into a miRNA-31 low-expression group and a miRNA-31 high-expression group. A survival curve was drawn according to the Kaplan-Meier method to evaluate the prognostic value of the circulating microRNA-31 expression levels for lung cancer. RESULTS: The circulating miRNA-31 expression levels in the lung cancer patients (l.88±0. 67) increased significantly (P<0.001) compared to the healthy controls (0.58±0. 44). The area under the ROC curve drawn according to the circulating miRNA-31 expression levels was 0.785 (95% CI=0.486-0.763). When the critical value was 1.27, the sensitivity and specificity for lung cancer diagnosis according to the circulating miRNA-31 expression levels were 0.769 and 0.745, respectively. The difference in the survival curve between the miRNA-31 low-expression group (123 cases) and high-expression group (177 cases) was statistically significant (P=0.004). Median survival period of the low-expression group (38.44 months) was longer than that of the high-expression group (25.23 months). CONCLUSIONS: miRNA-31 may be a molecular marker for the diagnostic and prognostic evaluation of primary lung cancer.

[Clinical analysis of the rare causes of hemoptysis: a report of 4 cases].

OBJECTIVE: To improve the diagnosis of hemoptysis caused by rare lung diseases. METHODS: Four cases of hemoptysis caused by rare diseases which were diagnosed by angiography or operation were reported and related literature were reviewed. RESULTS: The 4 cases of hemoptysis were caused by intercostal-to-pulmonary arterial fistula (IPAF), pulmonary hamartoma (PH), congenital unilateral absence of the left pulmonary artery (ALPA) and primary pulmonary hypertension (PPH). Bronchial arteriography and bronchial artery embolization were performed for IPAF. For PH, a benign tumor, the diagnosis was based on the history and radiography examination, and operation was the choice for therapy. ALPA was confirmed by radiography, if massive hemoptysis occurred, surgical intervention was the best choice. The diagnosis of PPH was firstly evaluated by chest film and echocardiogram, and the final diagnosis relied on right cardiac catheter examination. CONCLUSIONS: Hemoptysis is a common symptom of respiratory diseases, including some rare cases which are easy to be misdiagnosed. The correct diagnosis and therapy rely on comprehensive thinking, careful history collection and reasonable examinations.