Prognostic significance of huntingtin interacting protein 1 expression on patients with acute myeloid leukemia
| Autor: | Zhixin Ma, Mengxia Yu, Wenbin Qian, Hongyan Tong, Qi Guo, Xiufeng Yin, Hanzhang Pan, Qiu-Ling Ma, Yungui Wang, Jiansong Huang, Jie Jin, Chao Hu, Xia Li, Jinghan Wang, Haitao Meng, Dongmei Wang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine NPM1 Myeloid Kaplan-Meier Estimate Article Cohort Studies 03 medical and health sciences 0302 clinical medicine Cell Line Tumor CEBPA medicine Humans Gene silencing RNA Messenger RNA Small Interfering Cell Proliferation Regulation of gene expression Multidisciplinary Gene Expression Regulation Leukemic business.industry Gene Expression Profiling Reproducibility of Results Myeloid leukemia Huntingtin-interacting protein 1 Middle Aged Prognosis medicine.disease DNA-Binding Proteins Leukemia Myeloid Acute MicroRNAs Leukemia Treatment Outcome 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Multivariate Analysis Cancer research Female business Nucleophosmin |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep45960 |
| Popis: | Huntingtin interacting protein 1 (HIP1) is an endocytic protein which is overexpressed in a variety of human cancers and involved in cancer-causing translocation in leukemia. However, the prognostic impact of HIP1 expression on AML remains unclear. In this study, quantification of HIP1 transcript by real-time quantitative PCR in bone marrow blasts was performed in 270 AML patients. As a result, high HIP1 expression was seen more frequently in older patients, M4/M5 morphology and genes of NPM1 and DNMT3A mutations, and underrepresented in favorable karyotype subgroups and CEBPA double allele mutations in our AML patients. We also found high HIP1 expressers showed lower levels of hemoglobin. In addition, overexpression of HIP1 was associated with an inferior overall survival. The prognostic value of HIP1 expression was validated in patients from an independent TCGA cohort. Notably, up-regulation of miR-16, miR-15a, miR-28 and miR-660 were seen in high HIP1 expressers from the two independent cohorts. In vitro, interfereing of HIP1 expression by siRNA suppressed the proliferation of leukemic cells, and downregulation of these miRNAs were seen in THP-1 and Kasumi cell lines after silencing HIP1 expression. In conclusion, the HIP1 gene expression might serve as a reliable predictor for overall survival in AML patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|