miR-155: On the Crosstalk Between Inflammation and Cancer

Abstract

MicroRNAs are short non-coding RNAs that posttranscriptionally modulate the expression of multiple target genes and are thus implicated in a wide array of cellular and developmental processes. miR-155 is processed from BIC, a non-coding transcript highly expressed in both activated B and T cells and in monocytes/macrophages. miR-155 levels change dynamically during both hematopoietic lineage differentiation and the course of the immune response. Different mouse models developed recently indicate that miR-155 plays a critical role during hematopoiesis and regulates lymphocyte homeostasis and tolerance. A moderate increase of miR-155 levels is observed in many types of malignancies of B cell or myeloid origin, and transgenic over-expression of miR-155 in mice results in cancer. While the high levels of miR-155 reached transiently during the course of the immune response remain unharmful for the organism, the reason why a moderate up-regulation of miR-155 can lead to cancer remains obscure. As prolonged exposure to inflammation can lead to cancer, the permanent up-regulation of miR-155 might be a link between the two. Therefore, designing miR-155 based therapies will require a better understanding of the molecular basis of its action as well as of how miR-155 levels are regulated in a cell-specific manner.

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

“…Gerloff et al showed that NF‐κB can up‐regulate miR‐155 by binding on its promoter 51. Others have shown that constitutive up‐regulation of miR‐155 may mediate prolonged inflammatory reactions leading to cancer 18, 52. We previously showed a significant up‐regulation of miR‐155 in laryngopharyngeal mucosa treated by acidic bile accompanied by pre‐neoplastic lesions 10.…”

Interleukin-27 inhibits pediatric B-acute lymphoblastic leukemia cell spreading in a preclinical model

“…Furthermore, we showed that IL-27 downregulated miR-155 in B-ALL cells. MiR-155 has been reported to be expressed in activated B lymphocytes, 33 to be regulated in the course of immune responses 33 and to accumulate in human B-cell lymphomas. [34][35][36] In addition, studies on transgenic mice showed that miR-155 has a role in inducing a polyclonal expansion of preleukemic pre-B cells favoring the acquisition of secondary genetic changes for full transformation.…”

The altered expression of inflammation-related microRNAs with microRNA-155 expression correlates with Th17 differentiation in patients with acute coronary syndrome

“…miR-155 can be activated by the upstream activation of key transcription factors in traditional signaling pathways, like nuclear factor-kB and c-Jun N-terminal kinase; however, it may be regulated by related factors in other signaling pathways, such as Toll-like receptor, B-cell receptor and T-cell receptor signaling pathways as well as cytokines, such as IL-10. 22,23 Second, the reduction of circulating miR-155 in patients with ACS might be explained by the uptake of miR-155 by atherosclerotic lesions. 21 …”

“…Moreover, only certain transcripts were inhibited by miR-155 in specific cellular phases and microenvironments. 22 Therefore, in different physiological and pathological conditions, miR-155 might only directly inhibit certain transcripts and could play quite a different role in the differentiation of each Th cell subset. Smaand Mad-related protein 2 and suppressor of cytokine signaling 1, which are confirmed targets of miR-155, 34,35 may regulate Th17 cell differentiation in the opposite way.…”