Distinct associations of NEDD4L expression with genetic abnormalities and prognosis in acute myeloid leukemia

Abstract Background There is mounting evidence that demonstrated the association of aberrant NEDD4L expression with diverse human cancers. However, the expression pattern and clinical implication of NEDD4L in acute myeloid leukemia (AML) remains poorly defined. Methods We systemically determined NED...

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Autores principales:	Ming-qiang Chu, Liu-chao Zhang, Qian Yuan, Ting-juan Zhang, Jing-dong Zhou
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	NEDD4L Expression Prognosis Acute myeloid leukemia Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/3d41563e9f2a4d809e7465ad56c09c5d
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spelling	oai:doaj.org-article:3d41563e9f2a4d809e7465ad56c09c5d2021-11-28T12:36:52ZDistinct associations of NEDD4L expression with genetic abnormalities and prognosis in acute myeloid leukemia10.1186/s12935-021-02327-71475-2867https://doaj.org/article/3d41563e9f2a4d809e7465ad56c09c5d2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02327-7https://doaj.org/toc/1475-2867Abstract Background There is mounting evidence that demonstrated the association of aberrant NEDD4L expression with diverse human cancers. However, the expression pattern and clinical implication of NEDD4L in acute myeloid leukemia (AML) remains poorly defined. Methods We systemically determined NEDD4L expression with its clinical significance in AML by both public data and our research cohort. Moreover, biological functions of NEDD4L in leukemogenesis were further tested by in vitro experiments. Results By the public data, we identified that low NEDD4L expression was correlated with AML among diverse human cancers. Expression of NEDD4L was remarkably decreased in AML compared with controls, and was confirmed by our research cohort. Clinically, low expression of NEDD4L was correlated with greatly lower age, higher white blood cells, and higher bone marrow/peripheral blood blasts. Moreover, NEDD4L underexpression was positively correlated with normal karyotype, FLT3 and NPM1 mutations, but negatively associated with complex karyotype and TP53 mutations. Importantly, the association between NEDD4L expression and survival was also discovered in cytogenetically normal AML patients. Finally, a number of 1024 RNAs and 91 microRNAs were identified to be linked to NEDD4L expression in AML. Among the negatively correlated microRNAs, miR-10a was also discovered as a microRNA that may directly target NEDD4L. Further functional studies revealed that NEDD4L exhibited anti-proliferative and pro-apoptotic effects in leukemic cell line K562. Conclusions Our findings indicated that NEDD4L underexpression, as a frequent event in AML, was associated with genetic abnormalities and prognosis in AML. Moreover, NEDD4L expression may be involved in leukemogenesis with potential therapeutic target value.Ming-qiang ChuLiu-chao ZhangQian YuanTing-juan ZhangJing-dong ZhouBMCarticleNEDD4LExpressionPrognosisAcute myeloid leukemiaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	NEDD4L Expression Prognosis Acute myeloid leukemia Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	NEDD4L Expression Prognosis Acute myeloid leukemia Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Ming-qiang Chu Liu-chao Zhang Qian Yuan Ting-juan Zhang Jing-dong Zhou Distinct associations of NEDD4L expression with genetic abnormalities and prognosis in acute myeloid leukemia
description	Abstract Background There is mounting evidence that demonstrated the association of aberrant NEDD4L expression with diverse human cancers. However, the expression pattern and clinical implication of NEDD4L in acute myeloid leukemia (AML) remains poorly defined. Methods We systemically determined NEDD4L expression with its clinical significance in AML by both public data and our research cohort. Moreover, biological functions of NEDD4L in leukemogenesis were further tested by in vitro experiments. Results By the public data, we identified that low NEDD4L expression was correlated with AML among diverse human cancers. Expression of NEDD4L was remarkably decreased in AML compared with controls, and was confirmed by our research cohort. Clinically, low expression of NEDD4L was correlated with greatly lower age, higher white blood cells, and higher bone marrow/peripheral blood blasts. Moreover, NEDD4L underexpression was positively correlated with normal karyotype, FLT3 and NPM1 mutations, but negatively associated with complex karyotype and TP53 mutations. Importantly, the association between NEDD4L expression and survival was also discovered in cytogenetically normal AML patients. Finally, a number of 1024 RNAs and 91 microRNAs were identified to be linked to NEDD4L expression in AML. Among the negatively correlated microRNAs, miR-10a was also discovered as a microRNA that may directly target NEDD4L. Further functional studies revealed that NEDD4L exhibited anti-proliferative and pro-apoptotic effects in leukemic cell line K562. Conclusions Our findings indicated that NEDD4L underexpression, as a frequent event in AML, was associated with genetic abnormalities and prognosis in AML. Moreover, NEDD4L expression may be involved in leukemogenesis with potential therapeutic target value.
format	article
author	Ming-qiang Chu Liu-chao Zhang Qian Yuan Ting-juan Zhang Jing-dong Zhou
author_facet	Ming-qiang Chu Liu-chao Zhang Qian Yuan Ting-juan Zhang Jing-dong Zhou
author_sort	Ming-qiang Chu
title	Distinct associations of NEDD4L expression with genetic abnormalities and prognosis in acute myeloid leukemia
title_short	Distinct associations of NEDD4L expression with genetic abnormalities and prognosis in acute myeloid leukemia
title_full	Distinct associations of NEDD4L expression with genetic abnormalities and prognosis in acute myeloid leukemia
title_fullStr	Distinct associations of NEDD4L expression with genetic abnormalities and prognosis in acute myeloid leukemia
title_full_unstemmed	Distinct associations of NEDD4L expression with genetic abnormalities and prognosis in acute myeloid leukemia
title_sort	distinct associations of nedd4l expression with genetic abnormalities and prognosis in acute myeloid leukemia
publisher	BMC
publishDate	2021
url	https://doaj.org/article/3d41563e9f2a4d809e7465ad56c09c5d
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Distinct associations of NEDD4L expression with genetic abnormalities and prognosis in acute myeloid leukemia

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