Long non-coding RNA MALAT1 modulate cell migration, proliferation and apoptosis by sponging microRNA-146a to regulate CXCR4 expression in acute myeloid leukemia
| Autor: | Hui Li, Qiang Wen, Hai-Feng Zhuang, Xian-Fu Sheng, Fei-Yan Huang, Li-Li Hong |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Receptors CXCR4 Apoptosis Biology CXCR4 Young Adult 03 medical and health sciences 0302 clinical medicine Cell Movement hemic and lymphatic diseases medicine Humans Aged Cell Proliferation Aged 80 and over MALAT1 Gene Expression Regulation Leukemic Competing endogenous RNA Myeloid leukemia Cell migration Hematology Middle Aged medicine.disease Long non-coding RNA Leukemia Myeloid Acute MicroRNAs 030220 oncology & carcinogenesis Cancer research Adenocarcinoma Female RNA Long Noncoding 030215 immunology |
| Zdroj: | Hematology. 26:43-52 |
| ISSN: | 1607-8454 |
| DOI: | 10.1080/16078454.2020.1867781 |
| Popis: | To investigate the role of Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in acute myeloid leukemia (AML) and analyze the potential regulatory network of MALAT1/miR-146a/ CXCR4.The expressions of MALAT1, miR-146a and CXCR4 were performed by qRT-PCR and Western Blot. We conducted trans-well assay, CCK-8 assay and flow cytometry to evaluate the migration, proliferation and apoptosis of AML cells. Also by using luciferase reporter assay, we investigated the interaction between miR-146a and MALAT1 or CXCR4.Firstly, MALAT1 and CXCR4 were upregulated while miR-146a was downregulated in AML patients compared with healthy controls. We observed a negative correlation between miR-146a and MALAT1 or CXCR4, but a positive correlation between MALAT1 and CXCR4 in AML patients. MALAT1 knockdown inhibited migration and proliferation but induced apoptosis of HL-60 cells. MALAT1 restrained miR-146a expression by acting as a ceRNA. miR-146a regulated HL-60 cells migration, proliferation and apoptosis by directly targeting CXCR4 expression. Finally, we found that CXCR4 expression was downregulated by MALAT1 knockdown and partially restored by miR-146a abrogation.Our results showed that MALAT1 regulates migration, proliferation and apoptosis by sponging miR-146a to regulate CXCR4 expression in AML cells, providing novel insights into the role of MALAT1 as a therapeutic target in AML. |
| Databáze: | OpenAIRE |
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