Open AccessDownregulation of ENDOCAN in myeloid leukemia cells inhibits proliferation and promotes apoptosis by suppressing nuclear factor‑κB activity
Author(s) -
Lingling Sun,
Chengyu Sun,
Jiaying Sun,
Wenyan Yang
Publication year - 2019
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2019.9969
Subject(s) - myeloid leukemia , downregulation and upregulation , cell cycle , cancer research , k562 cells , u937 cell , gene silencing , leukemia , cell growth , apoptosis , gene knockdown , biology , cyclin d1 , microbiology and biotechnology , chemistry , immunology , biochemistry , gene
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.