LINC00665 promotes the progression of acute myeloid leukemia by regulating the miR-4458/DOCK1 pathway

Abstract

This study aimed to explore the role of LINC00665, miR-4458 and DOCK1 and their interactions in the development of acute myeloid leukemia (AML). The relative expression of LINC00665, miR-4458 and DOCK1 in AML samples was measured using qRT-PCR, and the protein level of DOCK1 in AML cell lines was examined using western blot. CCK8, BrdU, transwell, cell adhesion, and caspase-3 activity assays were carried out to evaluate the viability, proliferation, migration, adhesion, and apoptosis of AML cells, respectively. Luciferase reporter, RIP, and RNA pull-down assays were also performed to confirm the target relationship among LINC00665, miR-4458 and DOCK1. Findings revealed that LINC00665 and DOCK1 were aberrantly overexpressed in AML tissues and that the expression of miR-4458 was low in AML tissues. Silencing LINC00665 or DOCK1 presented significant restriction to the proliferation, migration and adhesion of AML cells. Apart from that, it was found that inhibiting miR-4458 could enhance the proliferation, migration and adhesion of AML cells but suppress the apoptosis of AML cells. Experimental results also indicated that LINC00665 exerted its positive function on AML cells by sponging miR-4458 and that miR-4458 influenced the progression of AML cells by targeting DOCK1 directly. Overall, this finding not only provided a novel molecular pathway for the diagnosis and treatment of AML but also showed that LINC00665 could enhance the progression of AML by regulating the miR-4458/DOCK1 pathway.

DNA Hypomethylation of DOCK1 Leading to High Expression Correlates with Neurologic Deterioration and Poor Function Outcomes after Spontaneous Intracerebral Hemorrhage

“…Not surprisingly, DOCK family members have been engaged in a variety of pathologies, including carcinogenesis and impairments in the central nervous and immune systems [ 13 ]. Recent literatures showed that DOCK1 overexpression may participate in tumor development and metastasis, including breast cancer [ 14 ], bladder cancer [ 15 ], and acute myeloid leukemia [ 16 ]. More specifically, DOCK1 could promote the IL8-induced chemotaxis and mesenchymal transition of glioma cells [ 17 ].…”

The new horizon of biomarker in melanoma patients

“…So far, only 4 arlncRNAs (LINC00665, [ 34 , 35 ] PCED1B-AS1, [ 36 , 37 ] LINC00324, [ 38 ] and ZEB1-AS1 [ 39 ] ) have been biologically validated in other tumors. However, as far as we know, these 9 arlncRNAs have not been fully validated in melanoma.…”

The Emerging Roles of LINC00665 in Human Cancers

“…Correlation analysis showed that the expression of LINC00665 was negatively correlated with miR-4458 in AML bone marrow tissue, and the results of qRT-PCR also displayed that miR-4458 was downregulated in AML tissue ( Yang et al, 2021b ). The luciferase reporter assay further proved that LINC00665 and miR-4458 could directly interact in AML cells ( Yang et al, 2021b ). Moreover, they demonstrated that LINC00665 promoted the proliferation, adhesion, and migration of AML cells but restricted the apoptosis of AML cells by sponging miR-4458 ( Yang et al, 2021b ).…”

“… Yang et al (2021b) revealed that LINC00665 was significantly upregulated in AML tissues and cell lines. Correlation analysis showed that the expression of LINC00665 was negatively correlated with miR-4458 in AML bone marrow tissue, and the results of qRT-PCR also displayed that miR-4458 was downregulated in AML tissue ( Yang et al, 2021b ). The luciferase reporter assay further proved that LINC00665 and miR-4458 could directly interact in AML cells ( Yang et al, 2021b ).…”