Long‐noncoding RNA HOTAIR inhibits immunologic rejection of mouse leukemia cells through activating the Wnt/β‐catenin signaling pathway in a mouse model of leukemia

Abstract

Long‐noncoding RNAs (lncRNAs) is involved in the development of diverse diseases, including leukemia, while the role lncRNA HOX transcript antisense RNA (HOTAIR) played in leukemia remains unclear and in need of further investigation. Therefore, this study was conducted to explore the effects of lncRNA HOTAIR on the immunologic rejection of leukemia cells through the Wnt/β‐catenin in mice. Mice were administrated with HOTAIR mimics as well as small interfering RNA HOTAIR to explore the regulatory role of HOTAIR. The numbers of white blood cell (WBC) and platelet (PLT) and the content of hemoglobin in peripheral blood (PB) were determined. The cytokine level in PB was measured. T‐lymphocyte proliferation activity, Ig production by B cells, natural killer (NK) cell activity, and the proportion of cluster of differentiation 4 (CD4)/CD8 T cell subsets were detected. Expression of HOTAIR, β‐catenin, cyclinD1, GSK‐3β, and c‐Myc in bone marrow was determined. It was revealed that the WBC number increased, while the PLT number along with the hemoglobin content in PB decreased with the upregulated HOTAIR. Additionally, elevated HOTAIR led to decreased levels of transforming growth factor‐β, interferon‐γ, interleukin‐10, and tumor necrosis factor‐α in PB, proliferation activity in T‐lymphocyte, and inhibited Ig production, NK cell activity, and the ratio of CD4/CD8 T cell subsets in B‐lymphocyte. Furthermore, Wnt/β‐catenin was activated by overexpressing HOTAIR. Enhanced survival and proliferation were shown with increased expression of cyclinD1, GSK‐3β, and c‐Myc in the bone marrow of mice induced by overexpressing HOTAIR. These results indicate that restored HOTAIR reduces the immunologic rejection of leukemia cells in mice by activating Wnt/β‐catenin pathway.

Functions of Exosomes in the Triangular Relationship between the Tumor, Inflammation, and Immunity in the Tumor Microenvironment

“…In addition, exosomes may also promote tumor progression in hematological cancers. For example, elevated levels of the lncRNA HOX transcript antisense (HOTAIR) can lead to decreased T-lymphocyte proliferation as well as reduced immunoglobulin production and a reversed ratio of CD4 + /CD8 + T cell subsets through the Wnt/ β -catenin pathway, which may eliminate the immunologic rejection of leukemia cells [37]. Exosomal circRNAs from tumor cells play a crucial role in poor prognosis in cancer [38]; however, few studies have examined their interaction with the immune system.…”

RETRACTED ARTICLE: Silencing lncRNA HOTAIR declines synovial inflammation and synoviocyte proliferation and promotes synoviocyte apoptosis in osteoarthritis rats by inhibiting Wnt/β-catenin signaling pathway

“…Hu et al have conveyed that HOTAIR together with other factors facilitates OA development through the Wnt/ β-catenin pathway [7]. Another study also suggested that up-regulated HOTAIR might activate the Wnt/βcatenin signaling pathway [9]. Interestingly, a latest study performed that HOTAIR performs as a new repressor of calcification genes and is downregulated by Wnt/β-catenin pathway in human aortic valve cells [10].…”

The Role of Long Non-coding RNAs in Immunotherapy Resistance

“…Finally, lncRNAs play a critical role in immune evasion. For example, HOTAIR not only promotes HLA-G expression to enhance the antigen presentation but also downregulates CD4+/CD8+ T-cell subsets (Figure 1; Table 1) (29, 30, 38), suggesting the dual effects of lncRNAs, which should be considered in future studies. These findings of immune-related lncRNAs in cancer immune regulation may provide potential theoretical strategies or novel approaches to overcome immune resistance through the manipulation of lncRNAs.…”