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LncRNA HOTTIP promotes proliferation and cell cycle progression of acute myeloid leukemia cells.

Abstract

OBJECTIVE

The aim of this study was to elucidate the biological function of long non-coding RNA (lncRNA) HOTTIP (HOXA transcript at the distal tip) in the development of acute myeloid leukemia (AML), and to investigate the potential mechanism.

PATIENTS AND METHODS

Relative expression levels of HOTTIP, microRNA-608 and DDA1 in AML patients were determined by quantitative Real-time polymerase chain reaction (qRT-PCR). Meanwhile, the expressions of these genes in AML cell lines were detected as well. The regulatory effects of HOTTIP, microRNA-608 and DDA1 on the proliferative ability and cell cycle progression of AML cells were examined by cell counting kit-8 (CCK-8) and flow cytometry, respectively. Dual-luciferase reporter gene assay was performed to confirm the binding condition of microRNA-608 to HOTTIP and DDA1. Finally, the specific role of HOTTIP/microRNA-608/DDA1 axis in the development of AML was verified through a series of rescue experiments.

RESULTS

HOTTIP was highly expressed in AML-M5 patients than normal controls. No significant difference in HOTTIP expression was found between patients with other subtypes of AML (M0, M1, M2, M3, M4 and M6) and normal controls. HOTTIP expression was significantly up-regulated in AML cell lines U-937 and THP-1. Up-regulation of HOTTIP remarkably promoted the proliferative potential and cell cycle progression of AML cells. Dual-luciferase reporter gene indicated that HOTTIP could bind to microRNA-608, which was lowly expressed in AML-M5 patients. Overexpression of microRNA-608 significantly inhibited the proliferative ability and cell cycle progression of U-937 and THP-1 cells. More importantly, microRNA-608 could partially reverse the regulatory effect of HOTTIP on AML cells. Meanwhile, DDA1 was verified as the target of microRNA-608. Subsequent experiments elucidated that DDA1 significantly accelerated the proliferation and cell cycle of AML cells. Furthermore, DDA1 could reverse the inhibitory effect of microRNA-608 on proliferative ability and cell cycle progression of AML cells.

CONCLUSIONS

HOTTIP accelerated the proliferative ability and cell cycle of AML cells via up-regulating DDA1 expression by sponging microRNA-608.

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  • Authors+Show Affiliations

    ,

    Department of Pediatrics, The Second People's Hospital of Liaocheng, Linqing, China. 573727123@qq.com.

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    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31002141

    Citation

    Zhuang, M-F, et al. "LncRNA HOTTIP Promotes Proliferation and Cell Cycle Progression of Acute Myeloid Leukemia Cells." European Review for Medical and Pharmacological Sciences, vol. 23, no. 7, 2019, pp. 2908-2915.
    Zhuang MF, Li LJ, Ma JB. LncRNA HOTTIP promotes proliferation and cell cycle progression of acute myeloid leukemia cells. Eur Rev Med Pharmacol Sci. 2019;23(7):2908-2915.
    Zhuang, M. F., Li, L. J., & Ma, J. B. (2019). LncRNA HOTTIP promotes proliferation and cell cycle progression of acute myeloid leukemia cells. European Review for Medical and Pharmacological Sciences, 23(7), pp. 2908-2915. doi:10.26355/eurrev_201904_17569.
    Zhuang MF, Li LJ, Ma JB. LncRNA HOTTIP Promotes Proliferation and Cell Cycle Progression of Acute Myeloid Leukemia Cells. Eur Rev Med Pharmacol Sci. 2019;23(7):2908-2915. PubMed PMID: 31002141.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - LncRNA HOTTIP promotes proliferation and cell cycle progression of acute myeloid leukemia cells. AU - Zhuang,M-F, AU - Li,L-J, AU - Ma,J-B, PY - 2019/4/20/entrez SP - 2908 EP - 2915 JF - European review for medical and pharmacological sciences JO - Eur Rev Med Pharmacol Sci VL - 23 IS - 7 N2 - OBJECTIVE: The aim of this study was to elucidate the biological function of long non-coding RNA (lncRNA) HOTTIP (HOXA transcript at the distal tip) in the development of acute myeloid leukemia (AML), and to investigate the potential mechanism. PATIENTS AND METHODS: Relative expression levels of HOTTIP, microRNA-608 and DDA1 in AML patients were determined by quantitative Real-time polymerase chain reaction (qRT-PCR). Meanwhile, the expressions of these genes in AML cell lines were detected as well. The regulatory effects of HOTTIP, microRNA-608 and DDA1 on the proliferative ability and cell cycle progression of AML cells were examined by cell counting kit-8 (CCK-8) and flow cytometry, respectively. Dual-luciferase reporter gene assay was performed to confirm the binding condition of microRNA-608 to HOTTIP and DDA1. Finally, the specific role of HOTTIP/microRNA-608/DDA1 axis in the development of AML was verified through a series of rescue experiments. RESULTS: HOTTIP was highly expressed in AML-M5 patients than normal controls. No significant difference in HOTTIP expression was found between patients with other subtypes of AML (M0, M1, M2, M3, M4 and M6) and normal controls. HOTTIP expression was significantly up-regulated in AML cell lines U-937 and THP-1. Up-regulation of HOTTIP remarkably promoted the proliferative potential and cell cycle progression of AML cells. Dual-luciferase reporter gene indicated that HOTTIP could bind to microRNA-608, which was lowly expressed in AML-M5 patients. Overexpression of microRNA-608 significantly inhibited the proliferative ability and cell cycle progression of U-937 and THP-1 cells. More importantly, microRNA-608 could partially reverse the regulatory effect of HOTTIP on AML cells. Meanwhile, DDA1 was verified as the target of microRNA-608. Subsequent experiments elucidated that DDA1 significantly accelerated the proliferation and cell cycle of AML cells. Furthermore, DDA1 could reverse the inhibitory effect of microRNA-608 on proliferative ability and cell cycle progression of AML cells. CONCLUSIONS: HOTTIP accelerated the proliferative ability and cell cycle of AML cells via up-regulating DDA1 expression by sponging microRNA-608. SN - 2284-0729 UR - https://www.unboundmedicine.com/medline/citation/31002141/LncRNA_HOTTIP_promotes_proliferation_and_cell_cycle_progression_of_acute_myeloid_leukemia_cells_ L2 - https://www.europeanreview.org/article/17569 DB - PRIME DP - Unbound Medicine ER -