Integrative omics analysis suggests a prognostic role and potential mechanisms of miro1 in multiple myeloma
Abstract
Multiple myeloma (MM) is a hematological malignancy for which a definitive cure remains elusive. Despite initial responses to treatment, most patients eventually develop drug resistance and experience relapse, which significantly compromises their prognosis. Miro1 (RHOT1), a small GTPase localised in the outer mitochondrial membrane, plays an important role in regulating mitochondrial dynamics. However, its specific function in tumour lipid metabolism has not been clarified. We investigated the role of Miro1 in MM by integrating transcriptomic and lipidomic profiling in Miro1-overexpressing MM cells (Karpas-707). RNA-seq and Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) were used to identify differentially expressed genes and lipid species, and population-level analyses including survival and Mendelian randomization (MR) were performed based on data from public available databases. Functional enrichment and statistical analyses were carried out using established bioinformatics pipelines. Overexpression of Miro1 induces significant transcriptional changes, with 114 differentially expressed genes enriched in pathways including lipid metabolism. Lipidomics analysis identified 33 altered lipid species, notably within the phosphatidylcholine (PC) category, though these differences lost statistical significance after FDR correction. Kaplan-Meier survival analysis demonstrated that elevated RHOT1 expression correlates with poor prognosis in multiple myeloma patients. Molecular covariate analysis further revealed a significant positive causal association between RHOT1 expression and four phospholipid species, indicating a mechanistic link between Miro1 and phospholipid metabolism in multiple myeloma. This integrated study reveals a novel role for Miro1 in the pathological pathways of multiple myeloma, potentially through regulation of phospholipid metabolism. By modulating lipid metabolic pathways, Miro1 may serve concurrently as both a prognostic biomarker and a potential therapeutic target in multiple myeloma.
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