Objective: Dysregulation of miR-592 has been reported in several tumors. However, its role in acute myeloid leukemia (AML) remains unknown. The present study aimed at investigating the expression pattern and biological function of miR-592 in AML and to elucidate the mechanism involved.
Patients and methods: qRT-PCR was used to analyze the expression of miR-592 in bone marrow and serum obtained from AML patients and healthy controls. The associations between serum miR-592 expression and clinical features and prognosis of AML patients were statistically analyzed. Then we detected the effect of miR-592 on proliferation, metastasis and apoptosis by CCK-8 assay, Transwell assays and flow cytometry, respectively. Dual-luciferase reporter assays were performed to validate the regulation of a putative target of miR-592. Rescue experiments were performed to confirm whether ROCK1 was a direct and functional target of miR-592 in AML.
Results: We found that the expression level of miR-592 was significantly lower in AML patients and AML cell lines. Low expression of serum miR-592 was associated with advanced French-American-British classification, cytogenetics and poor prognosis. Multivariate analysis confirmed that serum miR-592 expression was an independent prognostic factor for AML patients. Functionally, overexpression of miR-592 suppressed AML cell growth and metastasis, and promoted apoptosis. Further mechanistic investigation showed ROCK1 was a direct target gene of miR-592. Finally, ROCK1 overexpression rescued the effect of miR-592-mediated AML cell proliferation and metastasis.
Conclusions: These findings suggest that miR-592 acted as a tumor suppressor by targeting ROCK1 and may serve as a potential biomarker in AML.