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Genetic alterations in the cell cycle pathway are common in head and neck squamous cell carcinoma (HNSCC). We identified four novel HNSCC susceptibility loci (CDKN1C rs452338, CDK4 rs2072052, E2F2 rs3820028 and E2F2 rs2075993) through a two-stage matched case–control study. There was a combined effect among the four single nucleotide polymorphisms (SNPs), as the number of risk genotypes increased, the risk of HNSCC displayed an increasing trend (P trend < 0.001). And there were multiplicative interactions between rs452338 and rs2072052, rs2072052 and rs3820028, rs2072052 and rs2075993. Functional bioinformatics analysis and dual-luciferase reporter assay revealed that E2F2 rs2075993 T>C reduced the stability of E2F2 3'-UTR secondary structure and affected the binding of E2F2 to miR-940, which was up-regulated in HNSCC tumor tissues (P = 2.9e−8) and was correlated with poor overall survival of HNSCC (HR = 1.39, 95% CI = 1.02–1.90). In vitro assays, we discovered that the expression of miR-940 was regulated by METTL3 , and miR-940 promoted the proliferation, migration and invasion, and inhibited the senescence and autophagy of tumor cells. In terms of mechanism, compared with rs2075993 allele T, we found that the protective variant rs2075993 allele C interfered with the translational inhibition of E2F2 by miR-940, resulting in increased expression of E2F2 protein, which further reduced the proliferation, migration, invasion, and increased the senescence of tumor cells. [ABSTRACT FROM AUTHOR]

C-type lectin receptors (CLRs) are powerful pattern-recognition receptors that discern 'self' and 'non-self' in our body and protect us from invasive pathogens by mediating immune recognition and response. The gastrointestinal tract is very important for the maintenance of homeostasis; it is the largest shelter for the billions of microorganisms in the body and CLRs play a crucial regulatory role in this system. This study focuses on several CLRs, including Dectin-1, Dectin-2, Dectin-3 and Mincle. We summarize the roles of CLRs in maintaining gastrointestinal immune-system homeostasis, especially their functions in mediating immune recognition and responses in the gut, discuss their relationships to some diseases, highlight the significance of CLR-mediated sensing of microbial and non-microbial compounds in the gut immune system and identify new therapeutic targets. [ABSTRACT FROM AUTHOR]

Cytokine-induced killer (CIK) cells are immune effector cells characterized by co-expression of CD3 and CD56 molecules. We examined the quantities of CIK cells and the changes of these cell expressing NK cell receptors in HIV-1-positive children infected via mother-to-child transmission. The percentage of CIK cells was quantified and the changes in the surface cell receptor profiles in 18 HIV-1-infected children were examined. We found that CIK cell percentages were dramatically increased in HIV-1-infected children. Furthermore, the expressions of CD16, NKp30, NKp44, NKp46, NKp80 and CD244 on CIK cells were decreased, while the expressions of KIR3DL1 and NKG2D on CIK cells were increased in HIV-1-infected children. However, the expressions of KIR2D and NTB-A on CIK cells did not change in the HIV-1-infected children. CIK cells possessed the characteristics of promoting the maturation of dendritic cells and killing functions in HIV-1-infected children. Moreover, serum concentrations of IL-4 and IFN-γ were significantly increased in HIV-1-infected children compared with the HIV-negative controls. These changes likely occurred as a protective mechanism against transmission of maternal HIV-1 virus and thereby helped to limit viral spread, eliminate infected cells and help HIV-1-infected patients to slow the progression to AIDS. [ABSTRACT FROM PUBLISHER]

poptotic regulation is critical to organismal homeostasis and protection against many human disease processes such as cancer. Significant research efforts over the past several decades have illuminated many signaling molecules and effecter proteins responsible for this form of programmed cell death. Recent evidence suggests that transfer RNA (tRNA) regulates apoptotic sensitivity at the level of cytochrome c-mediated apoptosome formation. This finding unexpectedly places tRNA at the nexus of cellular biosynthesis and survival. Here we review the current understanding of both the apoptotic machinery and tRNA biology. We describe the evidence linking tRNA and cytochrome c in depth, and speculate on the implications of this link in cell biology. [ABSTRACT FROM AUTHOR]