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Down-regulation of miR-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabine
BACKGROUND: MicroRNA-29c (miR-29c) is abnormally expressed in several cancers and serves as an important predictor of tumor prognosis. Herein, we investigate the effects of abnormal miR-29c expression and analyze its clinical significance in acute myeloid leukemia (AML) patients. In addition, decita...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617691/ https://www.ncbi.nlm.nih.gov/pubmed/31333331 http://dx.doi.org/10.1186/s12935-019-0894-y |
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author | Tang, Li-juan Sun, Guo-kang Zhang, Ting-juan Wu, De-hong Zhou, Jing-dong Ma, Bei-bei Xu, Zi-jun Wen, Xiang-mei Chen, Qin Yao, Dong-ming Qian, Jun Ma, Ji-chun Lin, Jiang |
author_facet | Tang, Li-juan Sun, Guo-kang Zhang, Ting-juan Wu, De-hong Zhou, Jing-dong Ma, Bei-bei Xu, Zi-jun Wen, Xiang-mei Chen, Qin Yao, Dong-ming Qian, Jun Ma, Ji-chun Lin, Jiang |
author_sort | Tang, Li-juan |
collection | PubMed |
description | BACKGROUND: MicroRNA-29c (miR-29c) is abnormally expressed in several cancers and serves as an important predictor of tumor prognosis. Herein, we investigate the effects of abnormal miR-29c expression and analyze its clinical significance in acute myeloid leukemia (AML) patients. In addition, decitabine (DAC) has made great progress in the treatment of AML in recent years, but DAC resistance is still common phenomenon and the mechanism of resistance is still unclear. We further analyze the influences of miR-29c to leukemic cells treated with DAC. METHODS: Real-time quantitative PCR (RQ-PCR) was carried out to detect miR-29c transcript level in 102 de novo AML patients and 25 normal controls. miR-29c/shRNA-29c were respectively transfected into K562 cells and HEL cells. Cell viability after transfection was detected by cell counting Kit-8 assays. Flow cytometry was used to detect apoptosis. RESULTS: MiR-29c was significantly down-regulated in AML (P < 0.001). Low miR-29c expression was frequently observed in patients with poor karyotype and high risk (P = 0.006 and 0.013, respectively). Patients with low miR-29c expression had a markedly shorter overall survival (OS) than those with high miR-29c expression (P < 0.001). Multivariate analysis confirmed the independent prognostic value of low miR-29c expression in both the whole cohort as well as the cytogenetically normal AML (CN-AML) subset. Over-expression of miR-29c in K562 treated with DAC inhibited growth, while silencing of miR-29c in HEL promoted growth and inhibited apoptosis. MiR-29c overexpression decreased the half maximal inhibitory concentration (IC(50)) of DAC in K562, while miR-29c silencing increased the IC(50) of DAC in HEL. The demethylation of the miR-29c promoter was associated with its up-regulated expression. Although miR-29c demethylation was also observed in DAC-resistant K562 (K562/DAC), miR-29c expression was down-regulated. MiR-29c transfection also promoted apoptosis and decreased the IC(50) of DAC in K562/DAC cells. CONCLUSIONS: Our results suggest that miR-29c down-regulation may act as an independent prognostic biomarker in AML patients, and miR-29c over-expression can increase the sensitivity of both non-resistant and resistant of leukemic cells to DAC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-019-0894-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6617691 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-66176912019-07-22 Down-regulation of miR-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabine Tang, Li-juan Sun, Guo-kang Zhang, Ting-juan Wu, De-hong Zhou, Jing-dong Ma, Bei-bei Xu, Zi-jun Wen, Xiang-mei Chen, Qin Yao, Dong-ming Qian, Jun Ma, Ji-chun Lin, Jiang Cancer Cell Int Primary Research BACKGROUND: MicroRNA-29c (miR-29c) is abnormally expressed in several cancers and serves as an important predictor of tumor prognosis. Herein, we investigate the effects of abnormal miR-29c expression and analyze its clinical significance in acute myeloid leukemia (AML) patients. In addition, decitabine (DAC) has made great progress in the treatment of AML in recent years, but DAC resistance is still common phenomenon and the mechanism of resistance is still unclear. We further analyze the influences of miR-29c to leukemic cells treated with DAC. METHODS: Real-time quantitative PCR (RQ-PCR) was carried out to detect miR-29c transcript level in 102 de novo AML patients and 25 normal controls. miR-29c/shRNA-29c were respectively transfected into K562 cells and HEL cells. Cell viability after transfection was detected by cell counting Kit-8 assays. Flow cytometry was used to detect apoptosis. RESULTS: MiR-29c was significantly down-regulated in AML (P < 0.001). Low miR-29c expression was frequently observed in patients with poor karyotype and high risk (P = 0.006 and 0.013, respectively). Patients with low miR-29c expression had a markedly shorter overall survival (OS) than those with high miR-29c expression (P < 0.001). Multivariate analysis confirmed the independent prognostic value of low miR-29c expression in both the whole cohort as well as the cytogenetically normal AML (CN-AML) subset. Over-expression of miR-29c in K562 treated with DAC inhibited growth, while silencing of miR-29c in HEL promoted growth and inhibited apoptosis. MiR-29c overexpression decreased the half maximal inhibitory concentration (IC(50)) of DAC in K562, while miR-29c silencing increased the IC(50) of DAC in HEL. The demethylation of the miR-29c promoter was associated with its up-regulated expression. Although miR-29c demethylation was also observed in DAC-resistant K562 (K562/DAC), miR-29c expression was down-regulated. MiR-29c transfection also promoted apoptosis and decreased the IC(50) of DAC in K562/DAC cells. CONCLUSIONS: Our results suggest that miR-29c down-regulation may act as an independent prognostic biomarker in AML patients, and miR-29c over-expression can increase the sensitivity of both non-resistant and resistant of leukemic cells to DAC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-019-0894-y) contains supplementary material, which is available to authorized users. BioMed Central 2019-07-10 /pmc/articles/PMC6617691/ /pubmed/31333331 http://dx.doi.org/10.1186/s12935-019-0894-y Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Primary Research Tang, Li-juan Sun, Guo-kang Zhang, Ting-juan Wu, De-hong Zhou, Jing-dong Ma, Bei-bei Xu, Zi-jun Wen, Xiang-mei Chen, Qin Yao, Dong-ming Qian, Jun Ma, Ji-chun Lin, Jiang Down-regulation of miR-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabine |
title | Down-regulation of miR-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabine |
title_full | Down-regulation of miR-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabine |
title_fullStr | Down-regulation of miR-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabine |
title_full_unstemmed | Down-regulation of miR-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabine |
title_short | Down-regulation of miR-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabine |
title_sort | down-regulation of mir-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabine |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617691/ https://www.ncbi.nlm.nih.gov/pubmed/31333331 http://dx.doi.org/10.1186/s12935-019-0894-y |
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