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.
Background This study aimed to explain the effects and mechanism of MT1JP in lung cancer development and treatment. Material/Methods Thirty non-small cell lung cancer (NSCLC) (stages I–II, 17 cases; stages III–IV, 13 cases) and adjacent normal tissues were obtained. MT1JP and miRNA-423-3p levels were assessed by in situ hybridization and Bim protein expression by immunohistochemistry, and the correlations determined were analyzed. Cell proliferation was determined using MTT and colony formation assay, and cell apoptosis was measured using flow cytometry. A549 cell invasion and migration were assessed by Transwell migration and scratch wound healing assays. Relative mRNA and protein expressions were assessed using real-time polymerase chain reaction and western blotting. Correlations between miRNA-423-3p and Bim protein were investigated using luciferase activity assay, and Bim protein expression was evaluated using western blotting. Results MT1JP, miRNA-423-3p, and Bim expressions in NSCLC cancer tissues and those in adjacent cancer tissues were significantly different ( P <0.01 or P <0.001) with increasing stage. Compared with those in the normal control (NC) group, cell proliferation rates were significantly suppressed ( P <0.01 or P <0.001) and cell apoptosis rates significantly increased ( P <0.01 or P <0.001) in the miRNA inhibitor and lncRNA+miRNA inhibitor groups. Invasion cell numbers and wound healing rates were also significantly inhibited in the miRNA inhibitor and lncRNA+miRNA inhibitor groups ( P <0.01 or P <0.001) compared with those in the NC group. Conclusions The lncRNA MT1JP suppresses NSCLC biological activities by regulating the miRNA-423-3p/Bim axis.
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 LXRβ, one subtype of LXRs, can downregulate MMP-9 expression. More importantly, activation of LXRβ 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.
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