The role of disulfidptosis-associated LncRNA-LINC01137 in Osteosarcoma Biology and its regulatory effects on macrophage polarization

Abstract

The objective of this research is to investigate the function of long non-coding RNA (lncRNA) associated with disulfidptosis, particularly LINC01137, in osteosarcoma (OS), and its impact on macrophage polarization and the tumor immune microenvironment (TME), with the goal of identifying new prognostic biomarkers and therapeutic targets. Utilizing the OS transcriptome dataset from the TARGET database, differentially expressed lncRNAs related to disulfidptosis were identified. The functional mechanisms of LINC01137, which affect cell proliferation, migration, invasiveness, programmed cell death, and macrophage orientation, were explored using the full suite of analyses provided by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), alongside a diverse array of laboratory experiments, including an in vivo osteosarcoma xenograft model in BALB/c nude mice to assess the impact of LINC01137 knockdown on tumor growth. Among three lncRNAs identified that were distinctly linked to disulfidptosis, LINC01137 showed a notable increase in expression within OS cell lines. Silencing LINC01137 led to a marked decrease in the abilities of cell proliferation, migration, and invasiveness, simultaneously enhancing programmed cell death and facilitating the process of epithelial-mesenchymal transition (EMT). In vivo experiments further confirmed that LINC01137 knockdown significantly suppressed tumor growth in osteosarcoma xenograft models, aligning with the in vitro findings. Associated with disulfidptosis, LINC01137 is pivotal in osteosarcoma development through its enhancement of tumor cell proliferation, migration, and invasiveness, as well as its modification of macrophage orientation within the TME. Given its significance, LINC01137 merits exploration as a prognostic indicator, necessitating detailed studies on its regulatory functions and potential in therapy.

Keywords: Disulfidptosis; LncRNA LINC01137; Macrophage polarization; Osteosarcoma; Tumor immune microenvironment.