Down-regulation of miR-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabine
Abstract 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...
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doaj-57022728016c437b8be8e2047e0a58662020-11-25T03:01:03ZengBMCCancer Cell International1475-28672019-07-0119111110.1186/s12935-019-0894-yDown-regulation of miR-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabineLi-juan Tang0Guo-kang Sun1Ting-juan Zhang2De-hong Wu3Jing-dong Zhou4Bei-bei Ma5Zi-jun Xu6Xiang-mei Wen7Qin Chen8Dong-ming Yao9Jun Qian10Ji-chun Ma11Jiang Lin12Laboratory Center, Affiliated People’s Hospital of Jiangsu UniversityLaboratory Center, Affiliated People’s Hospital of Jiangsu UniversityLaboratory Center, Affiliated People’s Hospital of Jiangsu UniversityDepartment of Hematology, The Third People’s Hospital of Kunshan CityLaboratory Center, Affiliated People’s Hospital of Jiangsu UniversityLaboratory Center, Affiliated People’s Hospital of Jiangsu UniversityLaboratory Center, Affiliated People’s Hospital of Jiangsu UniversityLaboratory Center, Affiliated People’s Hospital of Jiangsu UniversityLaboratory Center, Affiliated People’s Hospital of Jiangsu UniversityLaboratory Center, Affiliated People’s Hospital of Jiangsu UniversityDepartment of Hematology, Affiliated People’s Hospital of Jiangsu UniversityLaboratory Center, Affiliated People’s Hospital of Jiangsu UniversityLaboratory Center, Affiliated People’s Hospital of Jiangsu UniversityAbstract 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 (IC50) of DAC in K562, while miR-29c silencing increased the IC50 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 IC50 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.http://link.springer.com/article/10.1186/s12935-019-0894-yMiR-29c expressionAcute myeloid leukemiaPrognosticDecitabine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Li-juan Tang Guo-kang Sun Ting-juan Zhang De-hong Wu Jing-dong Zhou Bei-bei Ma Zi-jun Xu Xiang-mei Wen Qin Chen Dong-ming Yao Jun Qian Ji-chun Ma Jiang Lin |
spellingShingle |
Li-juan Tang Guo-kang Sun Ting-juan Zhang De-hong Wu Jing-dong Zhou Bei-bei Ma Zi-jun Xu Xiang-mei Wen Qin Chen Dong-ming Yao Jun Qian Ji-chun Ma Jiang Lin Down-regulation of miR-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabine Cancer Cell International MiR-29c expression Acute myeloid leukemia Prognostic Decitabine |
author_facet |
Li-juan Tang Guo-kang Sun Ting-juan Zhang De-hong Wu Jing-dong Zhou Bei-bei Ma Zi-jun Xu Xiang-mei Wen Qin Chen Dong-ming Yao Jun Qian Ji-chun Ma Jiang Lin |
author_sort |
Li-juan Tang |
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_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_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_sort |
down-regulation of mir-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabine |
publisher |
BMC |
series |
Cancer Cell International |
issn |
1475-2867 |
publishDate |
2019-07-01 |
description |
Abstract 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 (IC50) of DAC in K562, while miR-29c silencing increased the IC50 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 IC50 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. |
topic |
MiR-29c expression Acute myeloid leukemia Prognostic Decitabine |
url |
http://link.springer.com/article/10.1186/s12935-019-0894-y |
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