MicroRNA-155-5p-dependent upregulation of PDCD4 is involved in oridonin-induced proliferation inhibition of leukemia cells
6 affiliations
- 1Department of Hematology, Children's Hospital Affiliated to Shandong University, Jinan, Shandong 250000, P.R. China
- 2Department of Hematology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250062, P.R. China
- 3Department of Hematology, Tengzhou Central People's Hospital, Zaozhuang, Shandong 277500, P.R. China
- 4Department of Immunology, School of Basic Medical Sciences, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
- 5Department of Blood Transfusion, Yantaishan Hospital Affiliated to Binzhou Medical University, Yantai, Shandong 264008, P.R. China
- 6Department of Laboratory Medicine, Zhangqiu District People's Hospital, Jinan, Shandong 250200, P.R. China
Abstract
As the antitumor mechanism of oridonin has not been clearly demonstrated, the effect of programmed cell death protein 4 (PDCD4) regulated by microRNA (miR)-155-5p on the proliferation of leukemia cells after exposure to oridonin was detected. The CCK-8 assay indicated that proliferation of the three kinds of leukemia cells was inhibited by oridonin, with the most significant inhibitory rate on HL60 cells compared with NB4 and U937 cells. Regarding the cell cycle profile, there was downregulation of the S phase, upregulation of the G2/M phase and no significant change in the G0/G1 phase. The downregulation of miR-155-5p was demonstrated by the differentially gene chromatin immunoprecipitation and verified using RT-qPCR in HL60 cells treated with oridonin. Compared with the oridonin group, the expression of miR-155-5p was restored after co-transfection of miRNA-155-5p mimics with oridonin, and the miR-55-5p inhibitor significantly downregulated the expression of miR-155-5p compared with the control group. The proliferation of HL60 cells was restored after simultaneous transfection of miR-55-5p mimics and treatment with oridonin and the miR-155-5p inhibitor could significantly downregulate proliferation of HL60 cells. After intersection analysis based on StarBase and miRDB, PDCD4 was identified to be a possible downstream apoptosis-related target gene. After exposure to oridonin, the expression of PDCD4 of HL60 cells was significantly upregulated and it was significantly decreased after simultaneous transfection of miR-155-5p mimics plus treatment with oridonin compared with the mimics control group and the proliferation level was restored. The targeted regulation of miR-155-5p on PDCD4 was demonstrated using a luciferase assay and miR-155-5p was negatively associated with PDCD4. The expression of PDCD4 was significantly downregulated after treatment with si-PDCD4 transfection together with oridonin compared with oridonin, which was accompanied by proliferation restoration of HL60 cells. Furthermore, apoptosis of HL60 cells was induced by oridonin, which was associated with the decrease of miR-155-5p and increase of PDCD4 that was verified using miR-155-5p mimics and si-PDCD4 transfection, respectively. The upregulation of the Bax/Bcl-2 ratio resulted in upregulation of cleaved caspase-3 and −9 expression, which was identified using a si-PDCD4 transfection assay. In conclusion, The miR-155-5p dependent upregulation of PDCD4 expression resulted in the increase of Bax/Bcl-2 ratio and activation of caspase-3 and −9, which contributed to the apoptosis of HL60 cells induced by oridonin.
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BibTeX
@article{ding2026microrna1555pdependent,
title = {{MicroRNA-155-5p-dependent upregulation of PDCD4 is involved in oridonin-induced proliferation inhibition of leukemia cells}},
author = {Hui Ding and Min Fang and Qingqing Yang and Chaozhe Wang and Yunhua Wu and Xidi Wang and Guosheng Jiang and Kehong Bi},
journal = {Oncology Letters},
year = {2026},
month = oct,
doi = {10.3892/ol.2026.15919},
url = {https://doi.org/10.3892/ol.2026.15919},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - MicroRNA-155-5p-dependent upregulation of PDCD4 is involved in oridonin-induced proliferation inhibition of leukemia cells
AU - Hui Ding
AU - Min Fang
AU - Qingqing Yang
AU - Chaozhe Wang
AU - Yunhua Wu
AU - Xidi Wang
AU - Guosheng Jiang
AU - Kehong Bi
PY - 2026
DA - 2026/10/23
JO - Oncology Letters
DO - 10.3892/ol.2026.15919
UR - https://doi.org/10.3892/ol.2026.15919
AB - As the antitumor mechanism of oridonin has not been clearly demonstrated, the effect of programmed cell death protein 4 (PDCD4) regulated by microRNA (miR)-155-5p on the proliferation of leukemia cells after exposure to oridonin was detected. The CCK-8 assay indicated that proliferation of the three kinds of leukemia cells was inhibited by oridonin, with the most significant inhibitory rate on HL60 cells compared with NB4 and U937 cells. Regarding the cell cycle profile, there was downregulation of the S phase, upregulation of the G2/M phase and no significant change in the G0/G1 phase. The downregulation of miR-155-5p was demonstrated by the differentially gene chromatin immunoprecipitation and verified using RT-qPCR in HL60 cells treated with oridonin. Compared with the oridonin group, the expression of miR-155-5p was restored after co-transfection of miRNA-155-5p mimics with oridonin, and the miR-55-5p inhibitor significantly downregulated the expression of miR-155-5p compared with the control group. The proliferation of HL60 cells was restored after simultaneous transfection of miR-55-5p mimics and treatment with oridonin and the miR-155-5p inhibitor could significantly downregulate proliferation of HL60 cells. After intersection analysis based on StarBase and miRDB, PDCD4 was identified to be a possible downstream apoptosis-related target gene. After exposure to oridonin, the expression of PDCD4 of HL60 cells was significantly upregulated and it was significantly decreased after simultaneous transfection of miR-155-5p mimics plus treatment with oridonin compared with the mimics control group and the proliferation level was restored. The targeted regulation of miR-155-5p on PDCD4 was demonstrated using a luciferase assay and miR-155-5p was negatively associated with PDCD4. The expression of PDCD4 was significantly downregulated after treatment with si-PDCD4 transfection together with oridonin compared with oridonin, which was accompanied by proliferation restoration of HL60 cells. Furthermore, apoptosis of HL60 cells was induced by oridonin, which was associated with the decrease of miR-155-5p and increase of PDCD4 that was verified using miR-155-5p mimics and si-PDCD4 transfection, respectively. The upregulation of the Bax/Bcl-2 ratio resulted in upregulation of cleaved caspase-3 and −9 expression, which was identified using a si-PDCD4 transfection assay. In conclusion, The miR-155-5p dependent upregulation of PDCD4 expression resulted in the increase of Bax/Bcl-2 ratio and activation of caspase-3 and −9, which contributed to the apoptosis of HL60 cells induced by oridonin.
SN - 1792-1074
SN - 1792-1082
ER -