Eur Rev Med Pharmacol Sci 2020; 24 (9): 4940-4953

DOI: 10.26355/eurrev_202005_21185

TUG1 weakens the sensitivity of acute myeloid leukemia cells to cytarabine by regulating miR-655-3p/CCND1 axis

B. Zhang, Y.-F. Sun, X.-M. Zhang, N. Jiang, Q. Chen

Department of Pediatrics, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan, China. nvkqrj@163.com


OBJECTIVE: Long non-coding RNA taurine upregulated gene 1 (lncRNA TUG1) has been demonstrated to promote malignant phenotypes and Adriamycin resistance in acute myeloid leukemia (AML) cells. However, the function and mechanism of TUG1 in cytarabine (Ara-C) sensitivity in AML remain unclear.

PATIENTS AND METHODS: Levels of TUG1, microRNA (miR)-655-3p or cyclin D1 (CCND1) mRNA were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation activity and apoptosis were analyzed using cell counting kit-8 (CCK-8) or flow cytometry, respectively. Western blot was utilized to detect the protein levels of Ki-67, B-cell lymphoma-2-associated X protein (Bax), and CCND1. The interaction between miR-655-3p and TUG1 or CCND1 was confirmed by Dual-Luciferase reporter and pull-down assay.

RESULTS: TUG1 and CCND1 were higher expressed, while miR-655-3p was lower expressed in AML cells compared with that in normal cells. Higher expression levels of TUG1 or CCND1, and lower expression levels of miR-655-3p both notably reversed Ara-C-induced proliferation inhibition and apoptosis promotion in AML cells. TUG1 was a sponge of miR-655-3p, and TUG1 knockdown enhanced the sensitivity of AML cells to Ara-C by regulating miR-655-3p. MiR-655-3p directly targeted CCND1, and CCND1 overexpression attenuated miR-655-3p restoration-mediated reinforcement of Ara-C sensitivity in AML cells. Besides that, TUG1 up-regulated CCND1 expression via miR-655-3p.

CONCLUSIONS: TUG1 weakened the sensitivity of AML cells to Ara-C by up-regulating CCND1 via miR-655-3p, suggesting a new insight into the chemotherapy of AML.

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To cite this article

B. Zhang, Y.-F. Sun, X.-M. Zhang, N. Jiang, Q. Chen
TUG1 weakens the sensitivity of acute myeloid leukemia cells to cytarabine by regulating miR-655-3p/CCND1 axis

Eur Rev Med Pharmacol Sci
Year: 2020
Vol. 24 - N. 9
Pages: 4940-4953
DOI: 10.26355/eurrev_202005_21185