Serum long non coding RNA MALAT-1 protected by exosomes is up-regulated and promotes cell proliferation and migration in non-small cell lung cancer

Circulating lncRNAs have been defined as a novel biomarker for non-small cell lung cancer (NSCLC), MALAT-1 was first identified lncRNA that was related to lung cancer metastasis. However, the relationship between exosomal lncRNAs and the diagnosis and prognosis of NSCLC was poorly understood. The ai...

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Veröffentlicht in:	Biochemical and biophysical research communications Jg. 490; H. 2; S. 406 - 414
Hauptverfasser:	Zhang, Rui, Xia, Yuhong, Wang, Zhixin, Zheng, Jie, Chen, Yafei, Li, Xiaoli, Wang, Yu, Ming, Huaikun
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Elsevier Inc 19.08.2017
Schlagworte:	60 APPLIED LIFE SCIENCES APOPTOSIS BIOLOGICAL MARKERS biomarkers blood serum Carcinoma, Non-Small-Cell Lung - blood Carcinoma, Non-Small-Cell Lung - diagnosis Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - pathology CELL CYCLE Cell Line, Tumor Cell Movement CELL PROLIFERATION COLONY FORMATION DIAGNOSIS Diagnostic marker Exosomes Exosomes - genetics Exosomes - pathology flow cytometry Gene Expression Regulation, Neoplastic HEALING Humans IN VITRO in vitro studies Lung - pathology lung neoplasms Lung Neoplasms - blood Lung Neoplasms - diagnosis Lung Neoplasms - genetics Lung Neoplasms - pathology LUNGS Lymphatic Metastasis - diagnosis Lymphatic Metastasis - genetics Lymphatic Metastasis - pathology MALAT-1 METASTASES metastasis Migration neoplasm cells NEOPLASMS non-coding RNA Non-small cell lung cancer PATIENTS Prognosis Proliferation RNA RNA, Long Noncoding - blood RNA, Long Noncoding - genetics small interfering RNA TUMOR CELLS Up-Regulation WOUNDS Diagnostic marker Proliferation Exosomes Migration Non-small cell lung cancer MALAT-1
ISSN:	0006-291X, 1090-2104, 1090-2104
Online-Zugang:	Volltext
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Abstract	Circulating lncRNAs have been defined as a novel biomarker for non-small cell lung cancer (NSCLC), MALAT-1 was first identified lncRNA that was related to lung cancer metastasis. However, the relationship between exosomal lncRNAs and the diagnosis and prognosis of NSCLC was poorly understood. The aim of this study is to evaluate the clinical significance of serum exosomal MALAT-1 as a biomarker in the metastasis of NSCLC. In this study, we firstly isolated the exosomes from healthy subjects and NSCLC patients. Then we measured the expression levels of MALAT-1 contained in exosomes, and found that exosomal MALAT-1 was highly expressed in NSCLC patients, more importantly, the levels of exosomal MALAT-1 were positively associated with tumor stage and lymphatic metastasis. In addition, we decreased MALAT-1 expression by short hairpin RNA and conducted a series of assays including MTT, cell cycle, colony formation, wound-healing scratch and Annexin/V PI by flow cytometry in human lung cancer cell lines. These in vitro studies demonstrated that serum exosome-derived long noncoding RNA MALAT-1 promoted the tumor growth and migration, and prevented tumor cells from apoptosis in lung cancer cell lines. Taken together, this study shed a light on utilizing MALAT-1 in exosomes as a non-invasive serum-based tumor biomarker for diagnosis and prognosis of NSCLC. •serum MALAT-1 contained in exosomes is upregulated in NSCLC patients.•Exosomal MALAT-1 was positively associated with TNM stage and lymphatic node metastasis.•MALAT-1 knockdown inhibited cell proliferation, colony formation and cell migration.•MALAT-1 knockdown induced cell cycle arrest and cell apoptosis.
AbstractList	Circulating lncRNAs have been defined as a novel biomarker for non-small cell lung cancer (NSCLC), MALAT-1 was first identified lncRNA that was related to lung cancer metastasis. However, the relationship between exosomal lncRNAs and the diagnosis and prognosis of NSCLC was poorly understood. The aim of this study is to evaluate the clinical significance of serum exosomal MALAT-1 as a biomarker in the metastasis of NSCLC. In this study, we firstly isolated the exosomes from healthy subjects and NSCLC patients. Then we measured the expression levels of MALAT-1 contained in exosomes, and found that exosomal MALAT-1 was highly expressed in NSCLC patients, more importantly, the levels of exosomal MALAT-1 were positively associated with tumor stage and lymphatic metastasis. In addition, we decreased MALAT-1 expression by short hairpin RNA and conducted a series of assays including MTT, cell cycle, colony formation, wound-healing scratch and Annexin/V PI by flow cytometry in human lung cancer cell lines. These in vitro studies demonstrated that serum exosome-derived long noncoding RNA MALAT-1 promoted the tumor growth and migration, and prevented tumor cells from apoptosis in lung cancer cell lines. Taken together, this study shed a light on utilizing MALAT-1 in exosomes as a non-invasive serum-based tumor biomarker for diagnosis and prognosis of NSCLC. - Highlights: • serum MALAT-1 contained in exosomes is upregulated in NSCLC patients. • Exosomal MALAT-1 was positively associated with TNM stage and lymphatic node metastasis. • MALAT-1 knockdown inhibited cell proliferation, colony formation and cell migration. • MALAT-1 knockdown induced cell cycle arrest and cell apoptosis. Circulating lncRNAs have been defined as a novel biomarker for non-small cell lung cancer (NSCLC), MALAT-1 was first identified lncRNA that was related to lung cancer metastasis. However, the relationship between exosomal lncRNAs and the diagnosis and prognosis of NSCLC was poorly understood. The aim of this study is to evaluate the clinical significance of serum exosomal MALAT-1 as a biomarker in the metastasis of NSCLC. In this study, we firstly isolated the exosomes from healthy subjects and NSCLC patients. Then we measured the expression levels of MALAT-1 contained in exosomes, and found that exosomal MALAT-1 was highly expressed in NSCLC patients, more importantly, the levels of exosomal MALAT-1 were positively associated with tumor stage and lymphatic metastasis. In addition, we decreased MALAT-1 expression by short hairpin RNA and conducted a series of assays including MTT, cell cycle, colony formation, wound-healing scratch and Annexin/V PI by flow cytometry in human lung cancer cell lines. These in vitro studies demonstrated that serum exosome-derived long noncoding RNA MALAT-1 promoted the tumor growth and migration, and prevented tumor cells from apoptosis in lung cancer cell lines. Taken together, this study shed a light on utilizing MALAT-1 in exosomes as a non-invasive serum-based tumor biomarker for diagnosis and prognosis of NSCLC. Circulating lncRNAs have been defined as a novel biomarker for non-small cell lung cancer (NSCLC), MALAT-1 was first identified lncRNA that was related to lung cancer metastasis. However, the relationship between exosomal lncRNAs and the diagnosis and prognosis of NSCLC was poorly understood. The aim of this study is to evaluate the clinical significance of serum exosomal MALAT-1 as a biomarker in the metastasis of NSCLC. In this study, we firstly isolated the exosomes from healthy subjects and NSCLC patients. Then we measured the expression levels of MALAT-1 contained in exosomes, and found that exosomal MALAT-1 was highly expressed in NSCLC patients, more importantly, the levels of exosomal MALAT-1 were positively associated with tumor stage and lymphatic metastasis. In addition, we decreased MALAT-1 expression by short hairpin RNA and conducted a series of assays including MTT, cell cycle, colony formation, wound-healing scratch and Annexin/V PI by flow cytometry in human lung cancer cell lines. These in vitro studies demonstrated that serum exosome-derived long noncoding RNA MALAT-1 promoted the tumor growth and migration, and prevented tumor cells from apoptosis in lung cancer cell lines. Taken together, this study shed a light on utilizing MALAT-1 in exosomes as a non-invasive serum-based tumor biomarker for diagnosis and prognosis of NSCLC. •serum MALAT-1 contained in exosomes is upregulated in NSCLC patients.•Exosomal MALAT-1 was positively associated with TNM stage and lymphatic node metastasis.•MALAT-1 knockdown inhibited cell proliferation, colony formation and cell migration.•MALAT-1 knockdown induced cell cycle arrest and cell apoptosis. Circulating lncRNAs have been defined as a novel biomarker for non-small cell lung cancer (NSCLC), MALAT-1 was first identified lncRNA that was related to lung cancer metastasis. However, the relationship between exosomal lncRNAs and the diagnosis and prognosis of NSCLC was poorly understood. The aim of this study is to evaluate the clinical significance of serum exosomal MALAT-1 as a biomarker in the metastasis of NSCLC. In this study, we firstly isolated the exosomes from healthy subjects and NSCLC patients. Then we measured the expression levels of MALAT-1 contained in exosomes, and found that exosomal MALAT-1 was highly expressed in NSCLC patients, more importantly, the levels of exosomal MALAT-1 were positively associated with tumor stage and lymphatic metastasis. In addition, we decreased MALAT-1 expression by short hairpin RNA and conducted a series of assays including MTT, cell cycle, colony formation, wound-healing scratch and Annexin/V PI by flow cytometry in human lung cancer cell lines. These in vitro studies demonstrated that serum exosome-derived long noncoding RNA MALAT-1 promoted the tumor growth and migration, and prevented tumor cells from apoptosis in lung cancer cell lines. Taken together, this study shed a light on utilizing MALAT-1 in exosomes as a non-invasive serum-based tumor biomarker for diagnosis and prognosis of NSCLC.Circulating lncRNAs have been defined as a novel biomarker for non-small cell lung cancer (NSCLC), MALAT-1 was first identified lncRNA that was related to lung cancer metastasis. However, the relationship between exosomal lncRNAs and the diagnosis and prognosis of NSCLC was poorly understood. The aim of this study is to evaluate the clinical significance of serum exosomal MALAT-1 as a biomarker in the metastasis of NSCLC. In this study, we firstly isolated the exosomes from healthy subjects and NSCLC patients. Then we measured the expression levels of MALAT-1 contained in exosomes, and found that exosomal MALAT-1 was highly expressed in NSCLC patients, more importantly, the levels of exosomal MALAT-1 were positively associated with tumor stage and lymphatic metastasis. In addition, we decreased MALAT-1 expression by short hairpin RNA and conducted a series of assays including MTT, cell cycle, colony formation, wound-healing scratch and Annexin/V PI by flow cytometry in human lung cancer cell lines. These in vitro studies demonstrated that serum exosome-derived long noncoding RNA MALAT-1 promoted the tumor growth and migration, and prevented tumor cells from apoptosis in lung cancer cell lines. Taken together, this study shed a light on utilizing MALAT-1 in exosomes as a non-invasive serum-based tumor biomarker for diagnosis and prognosis of NSCLC. Circulating lncRNAs have been defined as a novel biomarker for non-small cell lung cancer (NSCLC), MALAT-1 was first identified lncRNA that was related to lung cancer metastasis. However, the relationship between exosomal lncRNAs and the diagnosis and prognosis of NSCLC was poorly understood. The aim of this study is to evaluate the clinical significance of serum exosomal MALAT-1 as a biomarker in the metastasis of NSCLC. In this study, we firstly isolated the exosomes from healthy subjects and NSCLC patients. Then we measured the expression levels of MALAT-1 contained in exosomes, and found that exosomal MALAT-1 was highly expressed in NSCLC patients, more importantly, the levels of exosomal MALAT-1 were positively associated with tumor stage and lymphatic metastasis. In addition, we decreased MALAT-1 expression by short hairpin RNA and conducted a series of assays including MTT, cell cycle, colony formation, wound-healing scratch and Annexin/V PI by flow cytometry in human lung cancer cell lines. These in vitro studies demonstrated that serum exosome-derived long noncoding RNA MALAT-1 promoted the tumor growth and migration, and prevented tumor cells from apoptosis in lung cancer cell lines. Taken together, this study shed a light on utilizing MALAT-1 in exosomes as a non-invasive serum-based tumor biomarker for diagnosis and prognosis of NSCLC.
Author	Wang, Zhixin Chen, Yafei Zheng, Jie Wang, Yu Xia, Yuhong Li, Xiaoli Ming, Huaikun Zhang, Rui
Author_xml	– sequence: 1 givenname: Rui orcidid: 0000-0001-9592-465X surname: Zhang fullname: Zhang, Rui email: zhangruixx2015@sina.com organization: Respiratory Diseases Ward 2, The Central Hospital of Xinxiang City, Xinxiang, China – sequence: 2 givenname: Yuhong surname: Xia fullname: Xia, Yuhong organization: Respiratory Diseases Ward 2, The Central Hospital of Xinxiang City, Xinxiang, China – sequence: 3 givenname: Zhixin surname: Wang fullname: Wang, Zhixin organization: Respiratory Diseases Ward 2, The Central Hospital of Xinxiang City, Xinxiang, China – sequence: 4 givenname: Jie surname: Zheng fullname: Zheng, Jie organization: Thoracic Surgery Department 1, The Central Hospital of Xinxiang City, Xinxiang, China – sequence: 5 givenname: Yafei surname: Chen fullname: Chen, Yafei organization: Respiratory Diseases Ward 2, The Central Hospital of Xinxiang City, Xinxiang, China – sequence: 6 givenname: Xiaoli surname: Li fullname: Li, Xiaoli organization: Respiratory Diseases Ward 2, The Central Hospital of Xinxiang City, Xinxiang, China – sequence: 7 givenname: Yu surname: Wang fullname: Wang, Yu organization: Respiratory Diseases Ward 2, The Central Hospital of Xinxiang City, Xinxiang, China – sequence: 8 givenname: Huaikun surname: Ming fullname: Ming, Huaikun organization: Respiratory Diseases Ward 2, The Central Hospital of Xinxiang City, Xinxiang, China
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/28623135$$D View this record in MEDLINE/PubMed https://www.osti.gov/biblio/22719037$$D View this record in Osti.gov
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Keywords	Diagnostic marker Proliferation Exosomes Migration Non-small cell lung cancer MALAT-1
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Snippet	Circulating lncRNAs have been defined as a novel biomarker for non-small cell lung cancer (NSCLC), MALAT-1 was first identified lncRNA that was related to lung...
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SubjectTerms	60 APPLIED LIFE SCIENCES APOPTOSIS BIOLOGICAL MARKERS biomarkers blood serum Carcinoma, Non-Small-Cell Lung - blood Carcinoma, Non-Small-Cell Lung - diagnosis Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - pathology CELL CYCLE Cell Line, Tumor Cell Movement CELL PROLIFERATION COLONY FORMATION DIAGNOSIS Diagnostic marker Exosomes Exosomes - genetics Exosomes - pathology flow cytometry Gene Expression Regulation, Neoplastic HEALING Humans IN VITRO in vitro studies Lung - pathology lung neoplasms Lung Neoplasms - blood Lung Neoplasms - diagnosis Lung Neoplasms - genetics Lung Neoplasms - pathology LUNGS Lymphatic Metastasis - diagnosis Lymphatic Metastasis - genetics Lymphatic Metastasis - pathology MALAT-1 METASTASES metastasis Migration neoplasm cells NEOPLASMS non-coding RNA Non-small cell lung cancer PATIENTS Prognosis Proliferation RNA RNA, Long Noncoding - blood RNA, Long Noncoding - genetics small interfering RNA TUMOR CELLS Up-Regulation WOUNDS
Title	Serum long non coding RNA MALAT-1 protected by exosomes is up-regulated and promotes cell proliferation and migration in non-small cell lung cancer
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