Long non-coding RNA DANCR promotes the progression of non-small-cell lung cancer by inhibiting p21 expression.

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in human cancers. However, the functional roles of lncRNAs in non-small-cell lung cancer (NSCLC) and the underlying mechanisms are not well understood. METHODS: We examined the expression of lncRNA DANCR in NSCLC by qRT-PCR and explored its biological roles in NSCLC progression by cell and molecular biology studies. RESULTS: DANCR expression level was increased in human NSCLC. The knockdown of DANCR inhibited NSCLC cell proliferation by inducing cell apoptosis and cell cycle arrest. In addition, DANCR knockdown suppressed NSCLC cell migration and invasion via inhibition of epithelial-mesenchymal transition (EMT). On the contrary, DANCR overexpression had the opposite effects. DANCR knockdown inhibited EZH-2-mediated epigenetic silencing of p21 promoter and increased p21 expression. Moreover, DANCR knockdown inhibited NSCLC cell proliferation, migration, and invasion in a p21-dependent manner. CONCLUSION: DANCR plays oncogenic roles in NSCLC and may provide a novel biomarker for NSCLC diagnosis and prognosis.

Genetic polymorphisms of ERCC-1 and ERCC-2 are not prognostic markers in osteosarcoma patients with chemotherapy: A meta-analysis in Chinese population.

AIM: To make an accurate estimation of the association of ERCC1 and ERCC2 polymorphisms with osteosarcoma (OS) prognosis in Chinese population. METHODS: Total 7 qualified studies with 1404 osteosarcoma patients were included. Odds ratios (OR) with 95% CIs were pooled for the survival rate in different osteosarcoma patients with ERCC1 and ERCC2 genetic polymorphisms. The heterogeneity was assessed by I test. Potential publication bias was assessed by Begg funnel plot and Egger linear regression test. RESULTS: In rs11615, no significant association was found under dominant [TT+TC vs. CC: OR = 1.252, 95% CI:0.864-1.815, P = .235], recessive [TT vs. TC+CC: OR = 0.850, 95% CI: 0.695-1.030, P = .095] or allelic model [T vs. C Allele: OR = 1.219, 95% CI: 0.922-1.612, P = .165]. In rs13181, no significant association was found under dominant [AA+AC vs. CC: OR = 1.031, 95% CI: 0.800-1.329, P = .801], recessive [AA vs. AC+CC: OR = 1.005, 95% CI: 0.875, 1.154, P = .944] or allelic model [A vs. C Allele: OR = 1.009, 95% CI: 0.903-1.128, P = .870]. In rs1799793, no significant association was found under dominant [GG+GA vs. AA: OR = 1.134, 95% CI: 0.884-1.454, P = .322, recessive [GG vs. AG+AA: OR = 1.025, 95% CI: 0.881-1.192, P = .750], or allelic model [G vs. A Allele: OR = 1.046, 95% CI: 0.930-1.177, P = .450]. CONCLUSION: This study did not support rs11615, rs13181 or rs1799793 to be used as surrogate markers for clinical outcome of osteosarcoma with chemotherapy.

Tetrandrine suppresses ß­glucan­induced macrophage activation via inhibiting NF­κB, ERK and STAT3 signaling pathways.

Macrophages are important in inflammation through the production of various proinflammatory mediators. ß­glucan is a polymer of glucose, which is produced by numerous different organisms, including fungi, and acts as a trigger for the induction of inflammatory responses. Tetrandrine (TET), a bis­benzylisoquinoline alkaloid isolated from the Chinese herb Radix Stephania tetrandra, has been demonstrated to modulate inflammatory responses. In the present study, it was investigated whether TET affects the inflammatory reaction induced by ß­glucan in murine and human macrophages. It was demonstrated that ß­glucan induced the activation of nuclear factor (NF)­κB and markedly increased the levels of tumor necrosis factor­α (TNF­α) and interleukin 1 ß (IL­1ß) in macrophages. Treatment with TET resulted in downregulation of phosphorylated NF­κB p65 and reduction of the production of TNF­α and IL­1ß. In addition, the phosphorylation of ERK and STAT3 was decreased by TET in activated macrophages. Furthermore, it was demonstrated that the inhibitory effects of TET on ß­glucan­induced macrophage activation was not due to its cytotoxic action. Conclusively, these results indicate that TET can decrease the inflammatory responses mediated by ß­glucan in macrophages. Thus, TET may serve as an effective tool for the treatment of ß­glucan­associated inflammatory diseases.

LYN, a Key Gene From Bioinformatics Analysis, Contributes to Development and Progression of Esophageal Adenocarcinoma.

BACKGROUND Esophageal adenocarcinoma is a lethal malignancy whose incidence is rapidly growing in recent years. Previous reports suggested that Barrett's esophagus (BE), which is represented by metaplasia-dysplasia-carcinoma transition, is regarded as the premalignant lesion of esophageal neoplasm. However, our knowledge about the development of esophageal adenocarcinoma is still very limited. MATERIAL AND METHODS In order to acquire better understanding about the pathological mechanisms in this field, we obtained gene profiling data on BE, esophageal adenocarcinoma patients, and normal controls from the Gene Expression Omnibus (GEO) database. Bioinformatics analyses, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were conducted. RESULTS Our results revealed that several pathways, such as the wound healing, complement, and coagulation pathways, were closely correlated with cancer development and progression. The mitogen-activated protein kinase (MAPK) pathway was discovered to be responsible for the predisposition stage of cancer; while response to stress, cytokine-cytokine receptor interaction, nod-like receptor signaling pathway, and ECM-receptor interaction were chief contributors of cancer progression. More importantly, we discovered in this study that LYN was a critical gene. It was found to be the key nodule of several significant biological networks, which suggests its close correlation with cancer initiation and progression. CONCLUSIONS These results provided more information on the mechanisms of esophageal adenocarcinoma, which enlightened our way to the clinical discovery of novel therapeutic makers for conquering esophageal cancer.