MicroRNAs are beneficial for cancer therapy as they can simultaneously downregulate multiple targets involved in diverse biological pathways related to tumor development. In papillary thyroid cancer, many microRNAs were identified as differentially expressed factors in tumor tissues. In another way, recent studies revealed cell proliferation, cell cycling, apoptosis, and autophagy are critical pathways controlling papillary thyroid cancer development and progression. As miR‐524‐5p was approved as a cancer suppressor targeting multiple genes in several types of cancer cells, this study aims to characterize the role of miR‐524‐5p in the thyroid cancer cell. The expression of miR‐524‐5p was decreased in the papillary thyroid cancer tissues and cell lines, while forkhead box E1 (FOXE1) and ITGA3 were increased. In the clinical case, expression of miR‐524‐5p, FOXE1, and ITGA3 were significantly correlated with papillary thyroid cancer development and progression. FOXE1 and ITGA3 were approved as direct targets of miR‐524‐5p. miR‐524‐5p could inhibit papillary thyroid cancer cell viability, migration, invasion, and apoptosis through targeting FOXE1 and ITGA3. Cell cycling and autophagy pathways were disturbed by downregulation of FOXE1 and ITGA3, respectively. Collectively, miR‐524‐5p targeting on FOXE1 and ITGA3 prevents thyroid cancer progression through different pathways including cell cycling and autophagy.

G9a is a mammalian histone methyltransferase that contributes to the epigenetic silencing of tumor suppressor genes. Evidence suggests that G9a is required to maintain the malignant phenotype, but little documentation show the role of G9a function in mediating tumor growth. We retrospectively analyzed the protein of G9a and monomethylated histone H3 lysine 9 (H3K9 me1), and dimethylated histone H3 lysine 9 (H3K9 me2) in 175 cases of gastric carcinoma by immunohistochemistry. RNAi-based inhibition of G9a in MGC803 cancer cell line was studied. G9a depletion was done by transient transfection using Lipofectamine 2000. Depletion efficiency of G9a was tested using real-time PCR and western blot analysis. Cell apoptosis and proliferation were detected by TUNEL assay and MTT, respectively. The proteins of H3K9 me1, me2, trimethylation of H3K9 (H3K9 me3), monomethylated histone H3 lysine 27 (H3K27 me1), dimethylated histone H3 lysine 27 (H3K27 me2) and histone acetylated H3, apoptotic proteins were studied by western blot analysis. G9a and H3K9 me2 expression was higher in gastric cancer cells compared to the control (p<0.05). Both G9a and H3K9 me2 were positively correlated with the degree of differentiation, depth of infiltration, lymphatic invasions and tumor-node-metastasis stage in gastric carcinoma, (p<0.05). RNAi-mediated knockdown of G9a induced cell apoptosis and inhibited cell proliferation. Depletion of G9a reduced the levels of H3K9 me1 and me2, H3K27 me1 and me2. Nonetheless, it did not activate acetylation of H3 and H3K9 me3. These data suggest that G9a is required in tumorigenesis, and correlated with prognosis. Furthermore, G9a plays a critical role in regulating epigenetics. Depletion of G9a inhibits cell growth and induces cells apoptosis in gastric cancer. It might be of therapeutic benefit in gastric cancers.

The present study aimed to investigate the involvement of the Suv39H1 histone methyltransferase in the epigenetic changes in the euchromatic promoter in gastric carcinoma. We retrospectively analyzed the protein of Suv39H1 and tri-methylated histone H3 lysine 9 (H3K9) and histone H3 lysine 4 (H3K4) in 175 cases of gastric carcinoma by immunohistochemistry. Suv39H1 was depleted by siRNA, and cell apoptosis and cell proliferation were assessed by TUNEL and MTT assays, respectively. Histone methylated H3K9 and histone acetylated H3 and H4 were evaluated by western blotting. We found that the expression of Suv39H1 and tri-methylated H3K9 in gastric carcinoma was higher than that in benign gastric diseases (p<0.05). Tri-methylated H3K4 was similar in both tissue types (p>0.05). Both Suv39H1 and tri-methylated H3K9 were positively correlated with the degree of differentiation, depth of infiltration and lymphatic invasion (p<0.05) in gastric carcinoma. In addition, tri-methylated H3K9 was positively correlated with tumor stage, and node and metastatic statuses (p<0.05). Activation of Suv39H1 and overexpression of H3K9 tri-methylation may play an important role in tumorigenesis. They may be useful as a predictor for poor prognosis in gastric carcinoma. Silencing of the Suv39H1 gene decreased tri-methylated H3K9 and increased histone H3 acetylation, which caused activation of gene transcription, while there was no change in histone H4 acetylation. Depletion of Suv39H1 induced apoptosis and inhibited cell proliferation in the gastric cancer MGC803 cell line, while decreasing BCL-2, pro-caspase-9, pro-caspase-3 and C-myc. Suv39H1 may be a potential gene target for anti-gastric carcinoma therapy.

Summary Recurrence and diffuse infiltration challenge traditional therapeutic strategies for malignant glioma. Immunotherapy appears to be a promising approach to obtain long‐term survival. Dendritic cells (DCs), the most specialized and potent antigen‐presenting cells (APCs), play an important part in initiating and amplifying both the innate and adaptive immune responses against cancer cells. However, cancer cells can escape from immune surveillance by inhibiting maturation of DCs. Until the present, molecular mechanisms of maturation inhibition of DCs in the tumor microenvironment (TME) have not been fully revealed. Our study showed that pretreatment with tumor‐conditioned medium (TCM) collected from supernatant of primary glioma cells significantly suppressed the maturation of DCs. TCM pretreatment significantly changed the morphology of DCs, TCM decreased the expression levels of CD80, CD83, CD86 and interleukin (IL)‐12p70, while it increased the expression levels of IL‐10, transforming growth factor (TGF)‐β and IL‐6. RNA‐Seq showed that TCM pretreatment significantly increased the gene expression level of suppressor of cytokine signaling 1 (SOCS1) in DCs. suppressor of cytokine signaling 1 (SOCS1) knock‐down significantly antagonized the maturation inhibition of DCs by TCM, which was demonstrated by the restoration of maturation markers. TCM pretreatment also significantly suppressed T cell viability and T helper type 1 (Th1) response, and SOCS1 knock‐down significantly antagonized this suppressive effect. Further, TCM pretreatment significantly suppressed p65 nuclear translocation and transcriptional activity in DCs, and SOCS1 knock‐down significantly attenuated this suppressive effect. In conclusion, our research demonstrates that TCM up‐regulate SOCS1 to suppress the maturation of DCs via the nuclear factor‐kappa signaling pathway.