Abstract
Simple SummaryLeptomeningeal metastasis (LM) is a lethal complication in which cancer metastasizes to the meninges. Currently, there are neither definitive treatments nor diagnosis methods for LM patients. In this study, we suggest the examination of small non-coding RNA (smRNA) populations of extracellular vesicles (EVs) derived from the cerebrospinal fluid (CSF) as a potential vehicle for diagnosis and treatment strategies. Systemic and quantitative analysis of smRNA subpopulations from LM CSF EVs showed unique expression patterns between LM patients and healthy donors. In addition, LM CSF EVs smRNAs appeared to be associated with LM pathogenesis suggesting they may be viable targets for novel diagnostic and treatment strategies.Leptomeningeal metastasis (LM) is a fatal and rare complication of cancer in which the cancer spreads via the cerebrospinal fluid (CSF). At present, there is no definitive treatment or diagnosis for this deleterious disease. In this study, we systemically and quantitatively investigated biased expression of key small non-coding RNA (smRNA) subpopulations from LM CSF extracellular vesicles (EVs) via a unique smRNA sequencing method. The analyzed subpopulations included microRNA (miRNA), Piwi-interacting RNA (piRNA), Y RNA, small nuclear RNA (snRNA), small nucleolar RNAs (snoRNA), vault RNA (vtRNA), novel miRNA, etc. Here, among identified miRNAs, miR-21, which was already known to play an essential oncogenic role in tumorigenesis, was thoroughly investigated via systemic biochemical, miR-21 sensor, and physiological cell-based approaches, with the goal of confirming its functionality and potential as a biomarker for the pathogenesis and diagnosis of LM. We herein uncovered LM CSF extravesicular smRNAs that may be associated with LM-related complications and elucidated plausible pathways that may mechanistically contribute to LM progression. In sum, the analyzed smRNA subpopulations will be useful as targets for the development of therapeutic and diagnostic strategies for LM and LM-related complications.
Highlights
Leptomeningeal metastasis (LM) is a fatal and rare complication of cancer in which the cancer spreads to the meninges surrounding the brain and spinal cord via the cerebrospinal fluid (CSF) [1,2]
We found that small nuclear RNA (snRNA), small nucleolar RNAs (snoRNA), and vault RNA (vtRNA) were and vtRNA were detected to a much greater extent in LM CSF extracellular vesicles (EVs) compared to healthy control donors (HCs)
Our study revealed that the ratios of different types of extravesicular small non-coding RNA (smRNA) differed between LM patients and HC
Summary
Leptomeningeal metastasis (LM) is a fatal and rare complication of cancer in which the cancer spreads to the meninges surrounding the brain and spinal cord via the cerebrospinal fluid (CSF) [1,2]. CSF is a clear, colorless body fluid found in the brain and spinal cord. It is produced by specialized ependymal cells in the choroid plexuses of the ventricles of the brain [1]. As a potential vehicle for the spread of LM, CSF can be considered a good resource for the identification of new biological markers for the diagnosis derived from LM cells [6,7,8]
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