Pin1 inhibition exerts potent activity against acute myeloid leukemia through blocking multiple cancer-driving pathways

Journal of Hematology & Oncology
Xiaolan LianYuan-Zhong Chen

Abstract

The increasing genomic complexity of acute myeloid leukemia (AML), the most common form of acute leukemia, poses a major challenge to its therapy. To identify potent therapeutic targets with the ability to block multiple cancer-driving pathways is thus imperative. The unique peptidyl-prolyl cis-trans isomerase Pin1 has been reported to promote tumorigenesis through upregulation of numerous cancer-driving pathways. Although Pin1 is a key drug target for treating acute promyelocytic leukemia (APL) caused by a fusion oncogene, much less is known about the role of Pin1 in other heterogeneous leukemia. The mRNA and protein levels of Pin1 were detected in samples from de novo leukemia patients and healthy controls using real-time quantitative RT-PCR (qRT-PCR) and western blot. The establishment of the lentiviral stable-expressed short hairpin RNA (shRNA) system and the tetracycline-inducible shRNA system for targeting Pin1 were used to analyze the biological function of Pin1 in AML cells. The expression of cancer-related Pin1 downstream oncoproteins in shPin1 (Pin1 knockdown) and Pin1 inhibitor all-trans retinoic acid (ATRA) treated leukemia cells were examined by western blot, followed by evaluating the effects of genetic and chemic...Continue Reading

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Apr 25, 2019·Journal of Hematology & Oncology·Yaxian KongHong Zheng
Nov 16, 2019·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·S G KhoeiR Najafi
Jul 28, 2020·Science China. Life Sciences·Dongdong TiWeidong Han
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Dec 17, 2020·International Journal of Molecular Sciences·Jessica McAnulty, Analisa DiFeo
Mar 3, 2021·Blood·Marie-Claude GeoffroyHugues de Thé

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Methods Mentioned

BETA
PCR
transfection
FCS
flow cytometry
electrophoresis
xenograft
transmission electron microscopy
FACS

Software Mentioned

GraphPad Prism
ImageJ
SPSS

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