Objective: Multiple myeloma (MM) represents a common age-associated malignancy globally. The function and underlying mechanism of antisense lncRNA LBX2-AS1 remain ambiguous in multiple myeloma (MM). Herein, we aimed to observe the biological implication of this lncRNA in MM.Methods: RT-qPCR was employed to examine circulating LBX2-AS1 and LBX2 in 60 paired MM and healthy subjects. Correlation between the two was analyzed by Pearson test. Under transfection with shLBX2-AS1, proliferation and apoptosis were evaluated in MM cells through CCK-8, colony formation and flow cytometry. LBX2 expression was examined in MM cells with shLBX2-AS1 or pcDNA3.1-LBX2 transfection. Following treatment with cycloheximide or actinomycin D, LBX2 expression was examined in pcDNA3.1-LBX2-transfected MM cells at different time points. Rescue assays were then presented. Finally, xenograft tumor models were established.Results: Circulating LBX2-AS1 was up-regulated in MM patients and positively correlated to LBX2 expression. Area under the curve (AUC) of LBX2-AS1 expression was 0.7525. Its up-regulation was also found in MM cells and primarily distributed in cytoplasm. LBX2-AS1 knockdown distinctly weakened proliferative ability and induced apoptosis in MM cells. Overexpressing LBX2-AS1 markedly strengthened LBX2 expression by increasing its mRNA stability. Rescue assays showed that silencing LBX2-AS1 distinctly weakened the pcDNA3.1-LBX2-induced increase in proliferation and decrease in apoptosis for MM cells. Silencing LBX2-AS1 markedly weakened tumor growth.Conclusion: Our data demonstrated that circulating LBX2-AS1 could be an underlying diagnostic marker in MM. Targeting LBX2-AS1 suppressed tumor progression by affecting mRNA stability of LBX2 in MM. Hence, LBX2-AS1 could be a novel therapeutic marker against MM.
Objective: Multiple myeloma is an incurable hematological malignancy. It is imperative to identify immune markers for early diagnosis and therapy. Here, this study analyzed immune-related mRNAs and assessed their prognostic value and therapeutic potential.Methods: Abnormally expressed immune-related mRNAs were screened between multiple myeloma and normal bone marrow specimens in the GSE47552 and GSE6477 datasets. Their biological functions were then explored. Survival analysis was presented for assessing prognosis-related mRNAs. CIBERSORT was utilized for identifying 22 immune cell compositions of each bone marrow specimen. Correlation between FABP5 mRNA and immune cells was then analyzed in multiple myeloma.Results: Thirty-one immune-related mRNAs were abnormally expressed in multiple myeloma, which were primarily enriched in B cells-related biological processes and pathways. Following validation, FABP5 mRNA was a key risk factor of multiple myeloma. Patients with its up-regulation usually experienced unfavorable outcomes. There were distinct differences in the infiltration levels of B cells naïve, B cells memory, plasma cells, T cells CD4 naïve, resting memory CD4 T cells, activated memory CD4 T cells, Tregs, resting NK cells, M0 macrophages, M1 macrophages, M2 macrophages, and neutrophils between multiple myeloma and normal samples. FABP5 mRNA had correlations to B cells memory, B cells naïve, dendritic cells activated, macrophages M0, macrophages M1, macrophages M2, neutrophils, activated NK cells, resting memory CD4 T cells, CD8 T cells and Tregs.Conclusion: Collectively, our data showed that FABP5 mRNA was related to immune microenvironment, which could be a target of immunotherapy and prognostic marker for multiple myeloma.
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