IL‐4 and IL‐15 promotion of virtual memory CD8+ T cells is determined by genetic background

Virtual memory (VM) CD8⁺ T cells are present in unimmunized mice, yet possess T‐cell receptors specific for foreign antigens. To date, VM cells have only been characterized in C57BL/6 mice. Here, we assessed the cytokine requirements for VM cells in C57BL/6 and BALB/c mice. As reported previously, VM cells in C57BL/6 mice rely mostly on IL‐15 and marginally on IL‐4. In stark contrast, VM cells in BALB/c mice rely substantially on IL‐4 and marginally on IL‐15. Further, NKT cells are the likely source of IL‐4, because CD1d‐deficient mice on a BALB/c background have significantly fewer VM cells. Notably, this NKT/IL‐4 axis contributes to appropriate effector and memory T‐cell responses to infection in BALB/c mice, but not in C57BL/6 mice. However, the effects of IL‐4 are manifest prior to, rather than during, infection. Thus, cytokine‐mediated control of the precursor population affects the development of virus‐specific CD8⁺ T‐cell memory. Depending upon the genetic background, different cytokines encountered before infection may influence the subsequent ability to mount primary and memory anti‐viral CD8⁺ T‐cell responses.     

MiR-122-5p inhibits cell migration and invasion in gastric cancer by down-regulating DUSP4

Objective: To explore the relationship between miR-122-5p and DUSP4 and their effects on gastric cancer (GC) cell mobility and invasiveness.

Methods: Abnormally expressed miRNAs and mRNAs were analyzed using microarrays. The miR-122-5p and DUSP4 mRNA expression levels in GC tissues and cells were determined by RT-qPCR. The target relationship between miR-122-5p and DUSP4 was validated by dual luciferase reporter assay. GC cell mobility and invasiveness were respectively observed by wound healing assay and transwell invasion assay. Western blot and immunohistochemistry were used for detection of the expressions of DUSP4 protein and MMP2 and MMP9 proteins related to cell invasion and migration. The migration and invasion abilities of gastric cancer cells in vivo were evaluated according to the number of lung metastatic nodules in mice.

Results: The expression of miR-122-5p in GC tissues and cells was significantly down-regulated, whereas DUSP4 expression was up-regulated. Bioinformatics prediction strategies and dual luciferase reporter assay verified the binding sites of miR-122-5p on 3′UTR of DUSP4 and the target relationship between miR-122-5p and DUSP4. Overexpression of miR-122-5p and knockdown of DUSP4 in BGC-823 cells observantly suppressed GC cell mobility and invasiveness, whereas downregulation of miR-122-5p expression promoted cell metastasis. MiR-122-5p inhibited GC cell mobility and invasiveness and pulmonary tumor metastasis via downregulation of DUSP4.

Conclusion: MiR-122-5p restrained migration and invasion abilities of GC cells by repressing DUSP4.     

非酒精性脂肪肝患者血清miR-122的表达

目的探讨非酒精性脂肪肝(NAFLD)患者血清miR-122的表达水平,探索新的诊断NAFLD的生物学标记。方法选择临床确诊的NAFLD患者48例,健康对照组48例。留取血清,用实时荧光定量PCR方法检测血清miR-122的表达。统计学分析miR-122在两组间表达水平的差异。结果NAFLD患者血清miR-122的表达水平较对照组明显升高(P0.01)。结论miR-122可能参与了NAFLD的发病机制,有可能成为NAFLD新的诊断标记物。     

miR-122在胚胎干细胞/间充质干细胞诱导成肝细胞进程中的作用

miR-122是一种肝脏特异性microRNA,在肝脏发育过程中扮演重要作用.本文主要介绍miR-122在胚胎干细胞诱导成肝细胞进程中的作用,miR-122并不促进胚胎干细胞向定型内胚层细胞方向分化,然而促进定型内胚层细胞/肝前体细胞向肝细胞分化和成熟,此作用与肝富集转录因子、上皮间质转化等密切关联.     

Over-expression of MiR-122 promotes apoptosis of hepatocellular carcinoma via targeting TLR4

Introduction and objectiveMiR-122 has been regarded as a tumor suppressor. Toll-like receptor 4 (TLR4) has been found to be closely related to metastasis and immune escape of hepatocellular carcinoma (HCC). In the study, we sought to investigate the effect of miR-122 on HCC and the expression of TLR4.Patients or Materials and methodsReal-time PCR and Western blot were performed to detect the expressions of target factors. CCK-8 and flow cytometry analysis were employed to evaluate cell viability and apoptosis, respectively. Luciferase reporter assay was used to determine whether miR-122 could directly regulate the expression of TLR4. Enzyme-linked Immuno Sorbent Assay was adopted to detect the secretion of inflammatory cytokines.ResultsBoth down-regulation of miR-122 and up-regulation of TLR4 were found to be correlated with low overall survival rate of HCC patients. TLR4 may be a direct target gene of miR-122. Over-expression of miR-122 induced apoptosis and inhibited cell viability of HCC by down-regulating TLR4, enhanced the expression of pro-apoptotic genes and suppressed the expression of anti-apoptotic genes. MiR-122 inhibited expressions and activities of inflammatory cytokines, including vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), cyclooxygenase-2 (Cox-2) and prostaglandin E2 (PGE2) and also reduced the expression of matrix metallopeptidase 9 (MMP-9). Furthermore, activities of phosphatidylinositide 3-kinases (PI3K), Akt and nuclear factor-kappa B (NF-κB) were suppressed by miR-122.ConclusionsDown-regulation of miR-122 facilitated the immune escape of HCC by targeting TLR4, which was related to PI3K/Akt/NF-κB signaling pathways. Our study may provide a possible strategy for the treatment of HCC.