microRNA-145-3p inhibits non-small cell lung cancer cell migration and invasion by targeting PDK1 via the mTOR signaling pathway.

The mammalian target of rapamycin (mTOR) pathway is dysregulated in more than 50% of all human malignancies and is a major target in cancer treatment. In this study, we explored the underlying mechanism involving microRNA-145-3p (miR-145-3p) in the development and progression of non-small cell lung cancer (NSCLC) by targeting PDK1 via the mTOR signaling pathway. NSCLC tissues and adjacent normal tissues were obtained from 83 NSCLC patients. miR-145-3p, PDK1, and mTOR levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. Human NSCLC cell lines A549 and H1299 were transfected with miR-145-3p and siPDK1 to confirm the effect of miR-145-3p and PDK1 on NSCLC cells in vitro. Cell growth was evaluated by a CCK8 assay. Cell motility and chemotaxis analysis were determined by the scratch test and chemotaxis assay, respectively. The protein levels of PDK1 and mTOR were measured using the western blotting. Results showed lower level of miR-145-3p and higher levels of PDK1 and mTOR in NSCLC tissues compared to the adjacent normal tissues. In vitro results showed that cell growth, cell motility, and chemotaxis were all inhibited in cells transfected with miR-145-3p and those transfected with siPDK. Additionally, dual luciferase reporter gene assay helped confirmed that PDK1 is a target of miR-145. Finally, levels of PDK1, mTOR, and phosphorylated-mTOR were lower in cells transfected with miR-145-3p as well as those with siPDK1. These findings indicate that miR-145-3p may inhibit cell growth, motility, and chemotaxis in NSCLC by targeting PDK1 through suppressing the mTOR pathway.

Association between KIR gene polymorphisms and type 1 diabetes mellitus (T1DM) susceptibility: A PRISMA-compliant meta-analysis.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a T-cell mediated autoimmune disease with a complex genetic and immunological background. Evidence suggests that killer cell immunoglobulin-like receptor (KIR) genes are associated with T1DM, but the results are inconsistent. Here, we conducted a meta-analysis to comprehensively evaluate the effect of KIR genes on the risk of T1DM. METHODS: The PubMed, Web of Science, the Chinese Biomedical Database, and Chinese National Knowledge Infrastructure databases were systematically searched to select studies on the association between KIR polymorphisms and T1DM. The quality of each study was scoring in term of the Newcastle-Ottawa Scale. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of this association. Subgroup analysis stratified by ethnicity was also conducted. Funnel plot and Egger test were conducted to assess the publication bias. RESULTS: A total of 13 independent case-control studies comprising 2076 T1DM cases and 1967 controls were included in this meta-analysis. We found a negative association between the KIR2DL1 polymorphism and susceptibility to T1DM in the overall population (OR = 0.71, 95%CI = 0.51-0.98, P = .038), but not in ethnic-specific analysis. Additionally, a negative association between the KIR2DS1 polymorphism and susceptibility to T1DM was found in the Asians (OR = 0.76, 95%CI = 0.63-0.92, P = .004), but not in the Caucasians. However, the associations could not withstand Bonferroni correction. Conversely, no association between the other KIRs genes (KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL2, KIR3DL3, and KIR3DS1) and T1DM susceptibility was found in overall and subgroup ethnicity. No publication bias was detected in all comparisons. CONCLUSIONS: In summary, this meta-analysis suggested that the KIR2DL1 and 2DS1 polymorphism might be a potential protective factor for T1DM in the specific ethnicity. Further subtle design studies with more sample size are still needed for a definitive conclusion.