Biological Functions Of miR-155 Research Articles

Upregulated miR-155 inhibits inflammatory response induced by C. albicans in human monocytes derived dendritic cells via targeting p65 and BCL-10.

Candida albicans (C. albicans) is one of the most common fungal pathogens causing superficial and systemic infections. The innate immune system is the first defense line against C. albicans infection. MiR-155, a multifunctional microRNA (miRNA), has been proved to be a crucial regulator in innate immune response against bacterial and virus. However, the biological function of miR-155 in innate immune response against C. albicans infection remains unknown. The expression miR-155, as well as inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)], in monocytes derived dendritic cells (DCs) during heat-killed C. albicans infection was detected by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). The biological functions of miR-155 were investigated with "gain- and loss-of-function" experiments. Potential targets of miR-155 were identified by bioinformatics analysis, luciferase assay and western blot. Small interfering RNA (siRNA) was used to validate the function of miR-155 target. C. albicans increased the expression of miR-155 and pro-inflammatory factors. MiR-155 induced by C. albicans was depended on Dectin-1-spleen tyrosine kinase (Syk)/Raf-1-MAPK signaling pathway. Furthermore, miR-155 suppressed the secretion of pro-inflammatory cytokines induced by C. albicans by targeting NF-κB p65 and B cell leukemia/lymphoma 10 (BCL-10). In conclusion, up-regulated miR-155 acts as a negative feedback regulator in the innate immune response against C. albicans infection.

MicroRNA-155 promotes the proliferation of prostate cancer cells by targeting annexin 7.

Micro (mi)RNAs are a group of small non-coding RNA molecules that have been demonstrated to regulate the expression of genes involved in tumorigenesis. The relevance of microRNAs in the development, progression and prognosis of prostate cancer is not fully understood. miR-155 has been implicated in the induction of breast, lung and liver cancer, but its role in prostate cancer has not been investigated. In the present study, the biological function of miR-155 was investigated in prostate cancer for the first time, to the best of our knowledge. It was demonstrated that the expression of miR-155 was upregulated in prostate cancer tissues and cell lines as determined by quantitative reverse transcription-polymerase chain reaction. Furthermore, overexpression of miR-155 promoted cell proliferation, as indicated by MTT assay. Flow cytometric analysis demonstrated that inhibition of miR-155 induced cell cycle arrest and promoted apoptosis in prostate cancer cells. In addition, western blot analysis indicated that annexin (ANX)7 was significantly downregulated in prostate cancer tissues and cells. A luciferase reporter assay indicated that ANX7 was a target of miR-155, which suggested that miRNA-155 promoted the proliferation of prostate cancer cells by regulating ANX7 expression levels.

High expression of microRNA-155 is associated with the aggressive malignant behavior of gallbladder carcinoma

The prognosis of gallbladder cancer (GBC) remains poor despite recent advances in diagnostics and therapeutic strategies. Although the role of microRNAs (miRs) in GBC have not been well documented, miR-155 is known to be associated with inflammation-associated carcinogenesis in various types of cancers. The aim of this study was to investigate the clinical significance of miR-155 expression and the biological functions of miR-155 in GBC. The expression levels of miR-155 in surgically resected GBCs and gallbladders with pancreaticobiliary maljunction (PBM) were assessed by quantitative reverse transcription-polymerase chain reaction. The relationship between the expression levels of miR-155 and clinicopathological features of GBCs was analyzed. Human GBC cell lines were transfected with miR-155 inhibitors or mimics, and the effects on proliferation and invasion were assessed. miR-155 was significantly overexpressed in GBCs when compared with that in gallbladders with PBM (P=0.007) and normal gallbladders (P=0.04). The high expression level of miR-155 in GBCs was significantly associated with the presence of lymph node metastasis (P=0.01) and a poor prognosis (P=0.02). In vitro assays showed that aberrant expression of miR-155 significantly enhanced GBC cell proliferation and invasion. In conclusion, high miR-155 expression correlates with the aggressive behavior of GBCs, and miR-155 may become a prognostic marker and therapeutic target for GBC.

Inducible microRNA-155 Feedback Promotes Type I IFN Signaling in Antiviral Innate Immunity by Targeting Suppressor of Cytokine Signaling 1

Effective recognition of viral infection and subsequent triggering of antiviral innate immune responses are essential for the host antiviral defense, which is tightly regulated by multiple regulators, including microRNAs. Our previous study showed that a panel of microRNAs, including miR-155, was markedly upregulated in macrophages upon vesicular stomatitis virus infection; however, the biological function of miR-155 during viral infection remains unknown. In this paper, we show that RNA virus infection induces miR-155 expression in macrophages via TLR/MyD88-independent but retinoic acid-inducible gene I/JNK/NF-κB-dependent pathway. And the inducible miR-155 feedback promotes type I IFN signaling, thus suppressing viral replication. Furthermore, suppressor of cytokine signaling 1 (SOCS1), a canonical negative regulator of type I IFN signaling, is targeted by miR-155 in macrophages, and SOCS1 knockdown mediates the enhancing effect of miR-155 on type I IFN-mediated antiviral response. Therefore, we demonstrate that inducible miR-155 feedback positively regulates host antiviral innate immune response by promoting type I IFN signaling via targeting SOCS1.