Long non-coding RNA MALAT1 modulate cell migration, proliferation and apoptosis by sponging microRNA-146a to regulate CXCR4 expression in acute myeloid leukemia.
OBJECTIVES
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
['Sheng|Xian-Fu|XF|https://orcid.org/0000-0002-7317-965X', 'Hong|Li-Li|LL|https://orcid.org/0000-0001-7795-8223', 'Li|Hui|H|https://orcid.org/0000-0001-7467-4823', 'Huang|Fei-Yan|FY|https://orcid.org/0000-0003-4203-0534', 'Wen|Qiang|Q|https://orcid.org/0000-0003-3303-3389', 'Zhuang|Hai-Feng|HF|https://orcid.org/0000-0003-2802-7910']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D017209:Apoptosis D002465:Cell Movement D049109:Cell Proliferation D005260:Female D015973:Gene Expression Regulation, Leukemic D006801:Humans D015470:Leukemia, Myeloid, Acute D008297:Male D035683:MicroRNAs D008875:Middle Aged D062085:RNA, Long Noncoding D019718:Receptors, CXCR4 D055815:Young Adult
MALAT1 regulate CXCR4 Acute myeloid leukemia miR-146a HL-60 cells competing endogenous RNAs lncRNAs