MicroRNA-192 regulates cell proliferation and cell cycle transition in acute myeloid leukemia via interaction with CCNT2
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MicroRNAs (miRNAs) are a class of small non-coding RNAs approximately 18–22 nucleotides in length, which play an important role in malignant transformation. The roles of miR-192 as an oncogene or tumor suppressor in solid tumors have been previously reported. However, little is known about the role of miR-192 in human acute myeloid leukemia. The results of the present study indicate that miR-192 is significantly downregulated in specimens from acute myeloid leukemia patients. Functional assays demonstrated that overexpression of miR-192 in NB4 and HL-60 cells significantly inhibited cell proliferation compared with that in control cells, and induced G0/G1 cell cycle arrest, cell differentiation, and apoptosis in vitro. Dual-luciferase reporter gene assays showed that miR-192 significantly suppressed the activity of a reporter gene containing the wild type 3′-UTR of CCNT2, but it did not suppress the activity of a reporter gene containing mutated 3′-UTR of CCNT2. QRT-PCR and Western blot assays showed that miR-192 significantly downregulated the expression of CCNT2 in human leukemia cells. Exogenous expression of CCNT2 attenuated the cell cycle arrest induced by miR-192 in NB4 and HL-60 cells. Collectively, miR-192 inhibits cell proliferation and induces G0/G1 cell cycle arrest in AML by regulating the expression of CCNT2.
KeywordsmiR-192 Acute myeloid leukemia Cell cycle CCNT2
The authors thank the local doctors and the patients who participated in our study. The project was supported by the Hubei Provincial Natural Science Foundation of China (No. 2011CDD193).
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Conflicts of interest
The authors have declared no conflicts of interest.
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