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Tumor Discovery                                                       LCP2 regulates melanoma progression









































            Figure 5. Association between identified prognostic genes and TAL subsets and melanoma.
            TAL: Tumor-associated leukocyte.

            experiment showed that knockdown of LCP2 significantly   activation of inflammatory cytokines and chemokines that
            promoted the progression of melanoma in wild-type mice   are important for recruitment of T-cells [35,36] . Moreover,
            but had no effect on tumor sizes in nude mice, indicating the   the intratumoral IRF5 deletion in breast cancer cells
            negative correlation between LCP2 and melanoma growth,   dysregulated secretion of many chemokines and cytokines,
            as well as the importance of LCP2 in the tumor immune   leading to the inaccurate and untimely transport of immune
            microenvironment. The result of flow cytometry analysis   cells to the tumor sites . Takaoka et al. found that Irf5
                                                                                  [37]
            directly confirmed the positive correlation between LCP2   knockout mice were unable to secrete proinflammatory
            expression and CD8 T-cell activity. However, the pathway   cytokines (such as tumor necrosis factor α [TNF-α], IL-6,
                            +
            by which LCP2 regulates T-cell activity is unknown.  and IL-12), and exhibited resistance toward endotoxic
              To  explore  the  mechanism  through  which  LCP2   shock induced by lipopolysaccharide, indicating that IRF5
            regulates T-cell activity, DEGs of shLCP2 group versus   was generally involved in the downstream of TLR-MyD88
            control group were analyzed in this study, and we found   signaling pathway and induced the gene expression of
                                                                                      [38]
            that IRF5 expression was significantly downregulated.   proinflammatory cytokines . Moreover, studies  have
            Interferon regulatory factors (IRFs) are transcriptional   shown that most of the chemokines induced by virus in
            mediators of type 1 interferon signaling pathway induced   cells showed lymphocyte chemotactic activity in the case
                                                                                 [35]
            by pathogens and viruses, which are also involved in   of overexpression IRF5 , which therefore were significant
            immune response, apoptosis, cell growth regulation, and   for T-lymphocyte recruitment, indicating a possible key
            oncogenesis [29-31] . Some members of the IRFs have been   role of IRF5 in lymphocyte trafficking. Therefore, we
            shown to be involved in regulating development and   speculated the key bridge linking of IRF5 between LCP2
                                                                      +
            function of the immune cells [32-34] . IRF5, as a member of IRFs,   and CD8 T-cell. In our study, the expression of IRF5 was
            has been reported to play a key role in immune regulation   remarkably decreased in LCP2 knockdown B16F10 cells.
            of autoimmune diseases and inflammatory responses,   Taking together, we speculated that high expression of
            which therefore attracted much attention in recent years.   LCP2 in melanoma upregulated the IRF5 expression and
            In addition, it has been revealed that IRF5 is involved in the   IRF5 then mediated the secretion of proinflammatory


            Volume 2 Issue 1 (2023)                         9                           https://doi.org/10.36922/td.308
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