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Phosphatase of Regenerating liver-3 (PRL-3) Is Overexpressed in Classical Hodgkin Lymphoma and Promotes Survival and Migration

Magnus Aassved Hjort, Håkon Hov, Pegah Abdollahi, Esten Nymoen Vandsemb, Unn-Merete Fagerli, Bendik Lund, Tobias Schmidt Slørdahl, Magne Børset, Torstein Baade Rø

Exp Hematol Oncol. 2018 Apr 10;7:8.

PMID: 29651360

Abstract:

Background:
Phosphatase of regenerating liver-3 (PRL-3) is implicated in oncogenesis of hematological and solid cancers. PRL-3 expression increases metastatic potential, invasiveness and is associated with poor prognosis. With this study, we aimed to show a possible oncogenic role of PRL-3 in classical Hodgkin lymphoma (cHL).
Methods:
PRL-3 expression was measured in 25 cHL patients by immunohistochemistry and gene expression was analyzed from microdissected malignant cells. We knocked down PRL-3 in the cHL cell lines L1236 and HDLM2 and used small molecular inhibitors against PRL-3 to investigate proliferation, migration and cytokine production.
Results:
PRL-3 protein was expressed in 16% of patient samples. In three different gene expression datasets, PRL-3 was significantly overexpressed compared to normal controls. PRL-3 knockdown reduced proliferation, viability and Mcl-1 expression in L1236, but not in HDLM2 cells. Thienopyridone, a small molecule inhibitor of PRL-3, reduced proliferation of both L1236 and HDLM2. PRL-3 affected IL-13 secretion and enhanced STAT6 signaling. IL-13 stimulation partially rescued proliferation in L1236 cells after knockdown of PRL-3. PRL-3 knockdown reduced migration in both L1236 and HDLM2 cells.
Conclusion:
PRL-3 was overexpressed in a subset of cHL patients. Inhibition of PRL-3 increased IL-13 cytokine production and reduced migration, proliferation and viability. The effects could be mediated through regulation of the anti-apoptotic molecule Mcl-1 and a feedback loop of IL-13 mediated activation of STAT6. This point to a role for PRL-3 in the pathogenesis of Hodgkin lymphoma, and PRL-3 could be a possible new drug target.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP893449382 PRL-3 Inhibitor I PRL-3 Inhibitor I 893449-38-2 Price
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