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Molecular Signature of Extracellular Vesicular Small Non-Coding RNAs Derived from Cerebrospinal Fluid of Leptomeningeal Metastasis Patients: Functional Implication of miR-21 and Other Small RNAs in Cancer Malignancy

SIMPLE SUMMARY: Leptomeningeal 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 ext...

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Autores principales: Lee, Kyue-Yim, Seo, Yoona, Im, Ji Hye, Rhim, Jiho, Baek, Woosun, Kim, Sewon, Kwon, Ji-Woong, Yoo, Byong Chul, Shin, Sang Hoon, Yoo, Heon, Park, Jong Bae, Gwak, Ho-Shin, Kim, Jong Heon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828086/
https://www.ncbi.nlm.nih.gov/pubmed/33430103
http://dx.doi.org/10.3390/cancers13020209
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author Lee, Kyue-Yim
Seo, Yoona
Im, Ji Hye
Rhim, Jiho
Baek, Woosun
Kim, Sewon
Kwon, Ji-Woong
Yoo, Byong Chul
Shin, Sang Hoon
Yoo, Heon
Park, Jong Bae
Gwak, Ho-Shin
Kim, Jong Heon
author_facet Lee, Kyue-Yim
Seo, Yoona
Im, Ji Hye
Rhim, Jiho
Baek, Woosun
Kim, Sewon
Kwon, Ji-Woong
Yoo, Byong Chul
Shin, Sang Hoon
Yoo, Heon
Park, Jong Bae
Gwak, Ho-Shin
Kim, Jong Heon
author_sort Lee, Kyue-Yim
collection PubMed
description SIMPLE SUMMARY: Leptomeningeal 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. ABSTRACT: 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.
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spelling pubmed-78280862021-01-25 Molecular Signature of Extracellular Vesicular Small Non-Coding RNAs Derived from Cerebrospinal Fluid of Leptomeningeal Metastasis Patients: Functional Implication of miR-21 and Other Small RNAs in Cancer Malignancy Lee, Kyue-Yim Seo, Yoona Im, Ji Hye Rhim, Jiho Baek, Woosun Kim, Sewon Kwon, Ji-Woong Yoo, Byong Chul Shin, Sang Hoon Yoo, Heon Park, Jong Bae Gwak, Ho-Shin Kim, Jong Heon Cancers (Basel) Article SIMPLE SUMMARY: Leptomeningeal 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. ABSTRACT: 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. MDPI 2021-01-08 /pmc/articles/PMC7828086/ /pubmed/33430103 http://dx.doi.org/10.3390/cancers13020209 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Kyue-Yim
Seo, Yoona
Im, Ji Hye
Rhim, Jiho
Baek, Woosun
Kim, Sewon
Kwon, Ji-Woong
Yoo, Byong Chul
Shin, Sang Hoon
Yoo, Heon
Park, Jong Bae
Gwak, Ho-Shin
Kim, Jong Heon
Molecular Signature of Extracellular Vesicular Small Non-Coding RNAs Derived from Cerebrospinal Fluid of Leptomeningeal Metastasis Patients: Functional Implication of miR-21 and Other Small RNAs in Cancer Malignancy
title Molecular Signature of Extracellular Vesicular Small Non-Coding RNAs Derived from Cerebrospinal Fluid of Leptomeningeal Metastasis Patients: Functional Implication of miR-21 and Other Small RNAs in Cancer Malignancy
title_full Molecular Signature of Extracellular Vesicular Small Non-Coding RNAs Derived from Cerebrospinal Fluid of Leptomeningeal Metastasis Patients: Functional Implication of miR-21 and Other Small RNAs in Cancer Malignancy
title_fullStr Molecular Signature of Extracellular Vesicular Small Non-Coding RNAs Derived from Cerebrospinal Fluid of Leptomeningeal Metastasis Patients: Functional Implication of miR-21 and Other Small RNAs in Cancer Malignancy
title_full_unstemmed Molecular Signature of Extracellular Vesicular Small Non-Coding RNAs Derived from Cerebrospinal Fluid of Leptomeningeal Metastasis Patients: Functional Implication of miR-21 and Other Small RNAs in Cancer Malignancy
title_short Molecular Signature of Extracellular Vesicular Small Non-Coding RNAs Derived from Cerebrospinal Fluid of Leptomeningeal Metastasis Patients: Functional Implication of miR-21 and Other Small RNAs in Cancer Malignancy
title_sort molecular signature of extracellular vesicular small non-coding rnas derived from cerebrospinal fluid of leptomeningeal metastasis patients: functional implication of mir-21 and other small rnas in cancer malignancy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828086/
https://www.ncbi.nlm.nih.gov/pubmed/33430103
http://dx.doi.org/10.3390/cancers13020209
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