Downregulation of ENDOCAN in myeloid leukemia cells inhibits proliferation and promotes apoptosis by suppressing nuclear factor‑κB activity

Sun,Lingling; Sun,Chengyu; Sun,Jiaying; Yang,Wei

doi:10.3892/mmr.2019.9969

Downregulation of ENDOCAN in myeloid leukemia cells inhibits proliferation and promotes apoptosis by suppressing nuclear factor‑κB activity

Authors:
- Lingling Sun
- Chengyu Sun
- Jiaying Sun
- Wei Yang
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Affiliations: Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Anorectal Department, Shenyang Anorectal Hospital, Shenyang, Liaoning 110054, P.R. China, Intensive Care Unit, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China
Published online on: February 19, 2019 https://doi.org/10.3892/mmr.2019.9969
Pages: 3247-3254

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Abstract

Previous studies have demonstrated that ENDOCAN is elevated in leukemia, and it has been reported to be associated with poor prognosis. However, the functional role of ENDOCAN in the development of leukemia remains to be fully elucidated. In the present study, the expression levels of ENDOCAN were detected in THP‑1, U937, HL‑60 and K562 cells, and it was found that ENDOCAN was increased in U937 and K562 cells, compared with the other two cell lines. Subsequently, ENDOCAN was knocked down in U937 and K562 cells via lentiviral infection. It was found that cell proliferation and the expression of proliferating cell nuclear antigen were inhibited in myeloid leukemia cells following the silencing of ENDOCAN. ENDOCAN knockdown induced G0/G1‑phase cell cycle arrest in myeloid leukemia cells with a decreased expression of cyclin D1. Furthermore, cell apoptosis was increased in response to ENDOCAN silencing, which was accompanied by the downregulation of B‑cell lymphoma (BCL2) and the upregulation of BCL2‑associated X protein, cleaved caspases 3 and 9, and cleaved poly (ADP‑ribose) polymerase. Furthermore, it was demonstrated that the knockdown of ENDOCAN inhibited nuclear factor‑κB (NF‑κB) activity, as evidenced by the increased expression of NF‑κB inhibitor α (IκBα), decreased expression of phosphorylated (p‑)IκBα, p‑P65 and nuclear P65, and reduced NF‑κB DNA‑binding activity. In combination, the present findings suggested that ENDOCAN may serve as a potential therapeutic target in the treatment of leukemia.

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