miRNA mediated up-regulation of cochaperone p23 acts as an anti-apoptotic factor in childhood acute lymphoblastic leukemia.
p23 is a heat shock protein 90 (Hsp90) cochaperone that plays a significant role in estrogen receptor (ER) alpha signal transduction and telomerase activity; it is up-regulated in several cancers. Recent studies have found that high level of p23 may promote tumor progression and poor prognosis in breast cancer patients. p23 was found to be overexpressed in our previous microarray assay of 100 childhood acute lymphoblastic leukemia (ALL) bone marrow (BM) samples. In the present study, we verified the upregulation of p23 in clinical ALL samples, and identified p23 to be an anti-apoptotic factor in the process of chemotherapy. We also found that p23 was regulated by hsa-miR-101 which was down-regulated in childhood ALL cases. Altogether these data demonstrate that the misregulation of hsa-miR-101 contributes partly to the overexpression of p23 in childhood ALL. As an anti-apoptotic factor, p23 is able to be a potential target for anti-leukemic therapy.
Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Xiao
X
Liu
Limin
L
Zou
Lin
L
Zhu
Han
H
Zhang
Chaohao
C
Du
Zhigang
Z
Li
Chao
C
Gao
Xiaoxi
X
Zhao
Shilai
S
Bao
Huyong
H
Zheng
D000293:Adolescent; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D058990:Molecular Targeted Therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000071876:Prostaglandin-E Synthases; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D018841:HSP90 Heat-Shock Proteins; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases