Insulin receptor substrate 1 (IRS1), plays a critical role in insulin signaling and its control has an important place in the development of insulin resistance. The tyrosine phosphorylation of IRS1 serves as docking molecules for downstream effectors such as Phosphatidylinositol 3-kinase and phosphotyrosine phosphatase-2. We focused on the Gly972Arg and Ala513Pro variants of the IRS1 gene, since these specific allelic variants are located near the Tyr-Met-X-Met (YMXM) motifs around Tyr987 and Tyr612. Thus, we aimed to investigate the effects of Gly972Arg/Ala513Pro polymorphisms in IRS1 gene on development of insulin resistance and the risk of type 2 diabetes in a non-obese Turkish population. This work included 306 individuals comprising 178 subjects with type 2 diabetes and 128 healthy subjects matched for body mass index. Gly972Arg/Ala513Pro polymorphisms had no effect on type 2 diabetes risk and its phenotypes (P > 0.05). Although IRS1 gene and its variants are associated with type 2 diabetes and insulin resistance in several studies worldwide, our data showed that there is no association between Gly972Arg and Ala513Pro variants in IRS1 and disease in Turkish population.

Long non-coding RNAs (lncRNAs) have been implicated in numerous biological processes, including epigenetic regulation, cell-cycle control, and transcriptional/translational regulation of gene expression. Differential expression of lncRNAs and disruption of the regulatory processes are recognized as critical steps in cancer development. The role of lncRNAs in hepatitis B virus (HBV) infection is not well understood. Here we analyzed the expression of 135 lncRNAs in plasma samples of 82 HBV patients (classified as chronic patients, inactive carriers, or resolved patients) at diagnosis and at 12 months of treatment in relation to control group (81 healthy volunteers). We also investigated the effect of small interfering RNA (siRNA)-mediated silencing of lincRNA-SFMBT2 on HBV-positive human liver cancer cell line. lncRNA expression was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Chemically synthesized siRNAs were transfected into the cell lines using Lipofectamine 2000 Reagent (Thermo Fisher Scientific). HBV DNA and HBsAg and HBeAg were detected in transfected cultures by real-time PCR and ELISA, respectively, using commercial kits. We observed changes in lncRNA expression in all three HBV groups, compared to control group. Most notably, the expression of anti-NOS2A, lincRNA-SFMBT2, and Zfhx2as was significantly increased and expression of Y5 lncRNA was decreased in chronic HBV patients. A decreased Y5 expression and increased lincRNA-SFMBT2 expression were observed in inactive HBsAg carriers. The expression of HOTTIP, MEG9, and PCAT-32 was increased in resolved HBV patients, and no significant change in the expression of Y5 was observed, compared to control group. siRNA-mediated inhibition of lincRNA-SFMBT2 decreased the level of HBV DNA in human liver cancer cells. Further research is needed to confirm the prognostic as well as therapeutic role of these lncRNAs in HBV patients.

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The effect of Wnt pathway in head and neck cancer could not be elucidated, even though the aberrant Wnt signaling plays a key role in the development of many types of cancer. The inhibitor of β-catenin responsive transcription (ICRT-3) blocks the Wnt signaling pathway by binding to β-catenin, which is a coactivator of the Wnt signaling pathway and a promising agent for inhibiting aberrant signaling. In our study, we aimed to evaluate the effect of ICRT-3 on the cytotoxicity, apoptosis, cell cycle progression, migration, and gene expressions in head and neck cancer stem cell (HNCSC) and hypopharynx cancer. The effect of this compound on cytotoxicity and cell viability in FaDu and HNCSC line was assessed by using the water-soluble tetrazolium salt-1 method. The effect of ICRT-3 on apoptosis was detected by using Annexin V and caspase-3, caspase-9 kit, on cell cycle progression by cycle test plus DNA reagent kit, on gene expression by dual luciferase reporter assay, and on migration activity by wound healing assay in both cell lines. ICRT-3 was determined to have cytotoxic and apoptotic effect in both cell lines. In addition, it was also found that the administration of ICRT-3 caused cell cycle arrest and significant decrease in gene expression level and migration ability of the cells.

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