Associations between genetic variants located in mature microRNAs and risk of lung cancer.

MiRNAs have been focused for their wide range of biological regulatory functions. Previous studies have suggested that individual miRNAs could influence tumorigenesis through their regulation of specific proto-oncogenes and tumor suppressor genes. This study was implemented to investigate the associations between SNPs in mature microRNAs (miRNAs) and development of lung cancer in a two-stage, case-control study, followed by some functional validations. First, 11 SNPs were analyzed in a case-control study of lung cancer, and the significant results were validated in an additional population. Our results showed that rs3746444 in mir-499 (allele C vs T: OR = 1.33; 95% CI = 1.15-1.54; P = 1.2 × 10-4) and rs4919510 in mir-608 (allele G vs C: OR = 1.27; 95% CI= 1.13-1.43; P = 5.1 × 10-5) were significantly associated with increased risk of lung cancer. Rs3746444 in mir-499 was also significantly associated with poor survival of lung cancer (HR, 1.35; 95% CI, 1.15-1.58; P = 0.0002). The expression levels of mir-499 and mir-608 were significantly lower than those of adjacent normal tissues (P < 0.0005), and the carriers of minor alleles have lower expression levels of mir-499 and mir-608 than those of major alleles (P < 0.001). These findings indicated that rs3746444 in mir-499 and rs4919510 in mir-608 might play a substantial role in the susceptibility to lung cancer.

The possible molecular regulation mechanism of CIK cells inhibiting the proliferation of Human Lung Adenocarcinoma NCL-H157 Cells.

Cytokine-induced killer (CIK) cells were isolated and proliferation from human peripheral blood and cultured in appropriate growth medium. The biological characteristics of CIK cells were further determined by the characterization of surface markers by flow cytometry. CIK cells inhibited the proliferation of human lung adenocarcinoma NCL-H157 cells. Vascular endothelial growth factor (VEGF) expression was down-regulated in CIK cells co-cultured with NCL-H157 cells by western blotting analysis. Furthermore, in comparison with cells untreated by CIK, the NCL-H157 had a lower proliferation capacity. We proposed that the pharmacological mechanisms of NCL-H157 promoted by CIK can be estimated possibly with different biological significance that can be ascribed to down-regulated VEGF expression in vitro. The results suggest that the VEGF pathway guides developmental inhibiting of NCL-H157, and we speculate that the function of VEGF pathways is to guide NCL-H157 to inhibition by abundant CIK.

Effect of inhibition proliferation in human lung adenocarcinoma A549 cells by cytokine-induced killer cells.

BACKGROUND: Adenocarcinoma, the most common form of lung cancer, is one of main human malignant tumors. In this paper, we focus on the effect of antitumor activity of cytokine-induced killer (CIK) cells on human lung adenocarcinoma cell line A549. METHODS: CIK cells were obtained by inducing peripheral blood mononuclear cells with recombinant human (rh) interferon-gamma, monoclonal anti-CD3 antibody, rh interleukin (IL)-1alpha, and rhIL-2, which were added into the culture. A549 cell viability of CIK cells was determined using MTS assay. Flow cytometry (FCM) experiments were performed to detect cell cycle changes. The expression of P27 in A549 cells treated by CIK cells was evaluated by Western blot. RESULT: The percentage of CD3+CD16+CD56+ T cells in a representative peripheral blood mononucleated cell sample was 33.7 ± 1.3%. CIK cells, in dose and time dependent manners, inhibited the proliferation of A549. FCM demonstrated that A549 cells were accumulated in G2/M and G0/G1 phases when treated with CIK cells. FCM was used to analyze whether A549 cells treated with CIK cells induced apotosis or necrosis at 10:1 or 20:1. Compared to the control group, P27 was prominently upregulated in the CIK treated group. CONCLUSION: We propose that the pharmacological mechanisms of A549 cells inhibited by CIK cells can be estimated to possibly elicit different biological significance, which, in part, can be ascribed to a different mass transport rate in vitro.

MicroRNA-410 promotes cell proliferation by targeting BRD7 in non-small cell lung cancer.

miR-410 acts as an oncogene or tumor suppressor gene in some malignancies. However, its role in NSCLC is still unknown. In this study, we showed that the expression of miR-410 was up-regulated in both human NSCLC tissues and cells. Overexpression of miR-410 promoted cell proliferation, migration, and invasion of NSCLC. In addition, bromodomain-containing protein 7 (BRD7) was a direct target of miR-410. MiR-410-mediated downregulation of BRD7 led to increase Akt phosphorylation. Inhibition of Akt phosphorylation can rescue the effect of miR-410 on NSCLC cell. The expression of BRD7 was downregulated in NSCLC and was inversely expressed with miR-410 in NSCLC. Our data provided new knowledge regarding the role of miR-410 in the lung cancer progression.

Profiling the T-cell receptor repertoire of patient with pleural tuberculosis by high-throughput sequencing.

Pleural tuberculosis (PLTB), a major cause of morbidity and mortality, is the most common extrapulmonary manifestation of active Mycobacterium tuberculosis (Mtb) in developing countries. Gamma delta T-cell receptor (TCR) repertoire of peripheral blood mononuclear cells (PBMCs) and pleural effusion mononuclear cells (PEMCs) and beta TCR repertoire from peripheral blood mononuclear cells (PBMCs) have been reported. However, a detailed different characteristic of beta TCR repertoire of mononuclear cells isolated from peripheral blood and pleural fluid in the immune response to Mtb infection should be further revealed. The TCR ß-chain (TRB) from PBMCs and PEMCs from an untreated pleural tuberculosis patient was sequenced by the Illumina sequencing platform. A total of 96,758 and 124,130 unique complementarity-determining region 3 (CDR3) sequences were identified at the nucleotide level, encoding 69,488 and 99,095 peptide sequences, respectively. TCR profiling showed that TRBV20-1 family and TRBV20-1/TRBJ1-5 gene combination had a dominant expression in PEMCs, but not in PBMCs. Expansive expression of common CDR3 clonotypes was observed in PEMCs. CDR3 spectratyping analysis showed that few TRBV families had a significantly skewed pattern, with one peak or a few prominent peaks in the PBMCs. By contrast, some TRBV families showed oligoclonal or clonal expansion in the PEMCs. Here, we firstly profiled the TRB repertoire differences of PBMCs and PEMCs from one PLTB patient using high-throughput sequencing. And this study may provide new insight for the detailed and efficient study of TCR repertoire of PEMCs in the future.