Background: AURKA, Aurora kinase A encoding gene, is an important signaling hub gene for mitosis. In recent years, AURKA has been implicated in the occurrence and development of several cancers. However, its relationship with the tumor microenvironment in skin cutaneous melanoma (SKCM) and the molecular mechanisms underlying its effects are still unclear. Method：We adopted a variety of bioinformatics methods to comprehensively analyze the potential carcinogenesis of AURKA in SKCM, and constructed a prognostic nomogram model. We also dentified an inhibitor targeting AURKA and verified its therapeutic effects against SKCM using the molecular docking technology. Results:We found that abnormally high expression of AURKA was responsible for driving the occurrence and development of SKCM, and affected various pathological factors in SKCM. In addition, AURKA was established as an independent marker of poor SKCM prognosis. We also characterized the potential mechanisms by which AURKA manifests its effects in SKCM and found that AURKA inhibits the infiltration of CD8+ T cells and promotes hypoxia by activating the TGF-β signaling pathway. At the same time, the high AURKA expression group had higher tumor stemness index and promoted cell proliferation and metastasis. Finally, the small molecule compound ZNC97018978 targeting AURKA screened by molecular docking technology can inhibit the proliferation, invasion and metastasis of SKCM. The possible mechanism is that ZNC97018978 induces apoptosis by arresting the cell cycle, thereby inhibiting cell proliferation. Conclusion:AURKA is the core hub gene driving the occurrence and development of SKCM, and its expression is regulated by epigenetic modifications. AURKA can regulate the infiltration level of various immune cells in the tumor microenvironment, reshape the immunosuppressive tumor microenvironment, and apoptosis, and hypoxia. Thus, it is a prognostic biomarker and potential therapeutic target in SKCM. ZNC97018978 is an effective and safe inhibitor of AURKA in vitro; its safety and effectiveness in vivo as a potential treatment for cutaneous melanoma should be further determined.

Backgrounds: Absent in melanoma 2 (AIM2) is a crucial developmental regulator for innate immune responses and recent reports suggest its vital function in the process of cancer development and progression, however, the mutations, copy number variations (CNV), methylation, and relationship with the tumor microenvironment (TME), along with the underlying molecular biological processes, remain unclear. Methods: the mutations, CNVs, and methylation patterns of AIM2 in patients with skin cutaneous melanoma (SKCM) were systematically analyzed in this study. Its effects on TME, immunotherapy, and prognoses of SKCM patients were also investigated. According to the findings of the multifactorial Cox regression analysis, a prognostic alignment diagram-based model was constructed. Results: The findings showed that AIM2 expression differed significantly in patients with SKCM. The CNVs and gene methylation patterns affected the level of AIM2 expression, and genetic alterations could influence the tumor immunophenotype. The prognostic alignment diagram model had better predictive efficacy and may improve survival rates in patients. The elevated expression of AIM2 led to enhanced immune responses in SKCM patients and could induce cellular pyroptosis, apoptosis, and necrosis. AIM2 could promote CD8+ T-cell infiltration by activating the PANoptosis pathway and M1 macrophage polarization., and this may be a possible mechanism of its action. In addition, significant associations of AIM2 expression with hot tumor, tumor mutational burden (TMB), immune checkpoint-related genes, and microsatellite instability (MSI), were observed. Conclusions:AIM2 is associated with increased abundance of effector CD8+ T-cells, positive responses to immune checkpoint blockade (ICB) treatment, and improved prognoses. Therefore, it could be a putative enhancer and prognostic biomarker for the treatment of SKCM.

Background: AURKA, Aurora kinase A encoding gene, is an important signaling hub gene for mitosis. In recent years, AURKA has been implicated in the occurrence and development of several cancers. However, its relationship with the tumor microenvironment in skin cutaneous melanoma (SKCM) and the molecular mechanisms underlying its effects are still unclear. Method：We adopted a variety of bioinformatics methods to comprehensively analyze the potential carcinogenesis of AURKA in SKCM, and constructed a prognostic nomogram model. We also dentified an inhibitor targeting AURKA and verified its therapeutic effects against SKCM using the molecular docking technology. Results: We found that abnormally high expression of AURKA was responsible for driving the occurrence and development of SKCM, and affected various pathological factors in SKCM. In addition, AURKA was established as an independent marker of poor SKCM prognosis. We also characterized the potential mechanisms by which AURKA manifests its effects in SKCM and found that AURKA inhibits the infiltration of CD8+ T cells and promotes hypoxia by activating the TGF-β signaling pathway. At the same time, the high AURKA expression group had higher tumor stemness index and promoted cell proliferation and metastasis. Finally, the small molecule compound ZNC97018978 targeting AURKA screened by molecular docking technology can inhibit the proliferation, invasion and metastasis of SKCM. The possible mechanism is that ZNC97018978 induces apoptosis by arresting the cell cycle, thereby inhibiting cell proliferation. Conclusion: AURKA is the core hub gene driving the occurrence and development of SKCM, and its expression is regulated by epigenetic modifications. AURKA can regulate the infiltration level of various immune cells in the tumor microenvironment, reshape the immunosuppressive tumor microenvironment, and apoptosis, and hypoxia. Thus, it is a prognostic biomarker and potential therapeutic target in SKCM. ZNC97018978 is an effective and safe inhibitor of AURKA in vitro; its safety and effectiveness in vivo as a potential treatment for cutaneous melanoma should be further determined.

Backgrounds:Absent in melanoma 2 (AIM2) is a crucial developmental regulator for innate immune responses and recent reports suggest its vital function in the process of cancer development and progression, however, the mutations, copy number variations (CNV), methylation, and relationship with the tumor microenvironment (TME), along with the underlying molecular biological processes, remain unclear. Methods: the mutations, CNVs, and methylation patterns of AIM2 in patients with skin cutaneous melanoma (SKCM) were systematically analyzed in this study. Its effects on TME, immunotherapy, and prognoses of SKCM patients were also investigated. According to the findings of the multifactorial Cox regression analysis, a prognostic alignment diagram-based model was constructed. Results: The findings showed that AIM2 expression differed significantly in patients with SKCM. The CNVs and gene methylation patterns affected the level of AIM2 expression, and genetic alterations could influence the tumor immunophenotype. The prognostic alignment diagram model had better predictive efficacy and may improve survival rates in patients. The elevated expression of AIM2 led to enhanced immune responses in SKCM patients and could induce cellular pyroptosis, apoptosis, and necrosis. AIM2 could promote CD8+ T-cell infiltration by activating the PANoptosis pathway and M1 macrophage polarization., and this may be a possible mechanism of its action. In addition, significant associations of AIM2 expression with hot tumor, tumor mutational burden (TMB), immune checkpoint-related genes, and microsatellite instability (MSI), were observed. Conclusions:AIM2 is associated with increased abundance of effector CD8+ T-cells, positive responses to immune checkpoint blockade (ICB) treatment, and improved prognoses. Therefore, it could be a putative enhancer and prognostic biomarker for the treatment of SKCM.