Pan-Cancer Analysis Identifies AIMP2 as a Potential Biomarker for Breast Cancer

Abstract

Introduction:: Aminoacyl tRNA synthetase complex interacting with multifunctional protein 2 (AIMP2) is a significant regulator of cell proliferation and apoptosis. Despite its abnormal expression in various tumor types, the specific functions and effects of AIMP2 on tumor immune cell infiltration, proliferation, and migration remain unclear. background: AIMP2, Aminoacyl TRNA Synthetase Complex Interacting Multifunctional Protein 2, also known as JTV1, a multifunctional protein that forms a macromolecular complex with human aminoacyl tRNA synthetase, which consists of three non-enzymatic proteins, including p43, p38 and p18 proteins, of which p38 protein is AIMP2[1]. AIMP2 is necessary for the assembly and stability of aminoacyl tRNA synthetase complex[2]. Besides being important for efficient protein synthesis, additional physiological roles for AIMP2 have been discovered[3, 4]. For example, following DNA damage, AIMP2 is liberated from the ARS complex, phosphorylated in a JNK2-dependent pathway and translocated into the nucleus where it has been suggested to bind and sequester p53 from Mdm2-dependent ubiquitination[5]. AIMP2 has also been shown to be a substrate of E3 ligase Parkin[6]. Accumulation of AIMP2 as a result of Parkin mutation has been speculated to contribute to the characteristic dopaminergic cell death observed in Parkinson patients[7]. In addition, AIMP2 augments tumor necrosis factor-α-induced apoptotic signaling and exerts antiproliferative activities in TGF-β and Wnt pathways via distinct working mechanisms [8-10]. Therefore, we wonder that AIMP2 may play a crucial role in the occurrence and development of cancer. However, there are relatively few reseaches on AIMP2 in oncology. Current studies confirmed that AIMP2 may function as a multifunctional tumor suppressor[9, 11]. In this study, we analyzed the expression of AIMP2 and its relationship with the prognosis, Tumor Mutation Burden (TMB) and Microsatellite Instability (MSI) in 33 cancer types. In addition, we examined the correlation between AIMP2 and the immune microenvironment, immune-related antigens, and immune checkpoint genes. The results showed that AIMP2 was higher expressed in tumor tissue compared with normal tissue. Moreover, AIMP2 was associated with several tumor stages. Survival analysis showed that AIMP2 expression was strongly associated with OS in some cancer patients, where the high expression of AIMP2 was associated with a worse prognosis in five types of cancer. Then, we confirmed that the expression level of AIMP2 was associated with tumor immune infiltration and tumor microenvironment, especially in BRCA. Finally, si-RNA mediated knockdown of AIMP2 suppressed the proliferation and migration of BC cells in vitro. In conclusion, AIMP2 was found to be differentially expressed in the pan-cancer analysis and might play an important role in tumor immunity, which is expected to be a potential tumor prognostic marker, especially in BRCA. Method:: To assess AIMP2's role in tumor immunity, we conducted a pan-cancer multi-database analysis using the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Lines Encyclopedia (CCLE) datasets, examining expression levels, prognosis, tumor progression, and immune microenvironment. Additionally, we investigated AIMP2's impact on breast cancer (BRCA) proliferation and migration using cell counting kit 8 (CCK-8) assay, transwell assays, and western blot analysis. objective: In order to evaluate the role of AIMP2 in tumor immunity in a pan-cancer multi-database. Result:: Our findings revealed that AIMP2 was overexpressed in 24 tumor tissue types compared to normal tissue and was associated with four tumor stages. Survival analysis indicated that AIMP2 expression was strongly correlated with overall survival (OS) in certain cancer patients, with high AIMP2 expression linked to poorer prognosis in five cancer types. Conclusion:: Finally, siRNA-mediated AIMP2 knockdown inhibited BRCA cell proliferation and migration in vitro. In conclusion, our pan-cancer analysis suggests that AIMP2 may play a crucial role in tumor immunity and could serve as a potential prognostic marker, particularly in BRCA. conclusion: AIMP2 was found to be differentially expressed in the pan-cancer analysis and might play an important role in tumor immunity, which is expected to be a potential tumor prognostic marker, especially in BRCA. other: -