Abstract
Mantle cell lymphoma (MCL) is highly aggressive and its treatment remains challenging, understanding its pathogenesis is critical for future targeted therapy. SUMO specific proteases 1 (SENP1) is an important protein that regulates the balance between SUMOylation and deSUMOylation. We found that SENP1 was upregulated in MCL patient samples and cell lines. Knockdown of SENP1 could inhibit the proliferation and promote the apoptosis of MCL cells. We also found that SENP1 knockdown caused inhibition of the JAK-STAT5 pathway and upregulation of tumor suppressor cytokine signaling 2 (SOCS2). Moreover, MCL tumor growth in vivo was significantly suppressed after SENP1 knockdown in a xenograft nude mouse model. In summary, our results showed that SENP1 is involved in the pathogenesis of MCL and may be a potential therapeutic target.
Highlights
Mantle-cell lymphoma (MCL) is a highly malignant and aggressive B-cell non-Hodgkin’s lymphoma (NHL) which accounts for 5–10% of all NHL [1]
We found SENP1 was upregulated in Mantle cell lymphoma (MCL) patient samples and cell lines; knockdown of SENP1 inhibited MCL cell proliferation and promoted cell apoptosis, and inhibited MCL tumor growth in mice; mechanically, knockdown of SENP1 resulted in an increased expression of tumor suppressor cytokine signaling 2 (SOCS2) by inhibiting the JAK-STAT5 activity
SENP1 is upregulated in mantle cell lymphoma To test the expression of SENP1 in MCL, we firstly detected the expression of SENP1 in human MCL specimens and reactive lymph node enlargement specimens by immunohistochemistry, which showed that the SENP1 protein expression in the MCL specimens was significantly higher than that in the reactive lymph node enlargement specimens (Fig. 1A, B)
Summary
Mantle-cell lymphoma (MCL) is a highly malignant and aggressive B-cell non-Hodgkin’s lymphoma (NHL) which accounts for 5–10% of all NHL [1]. SUMOylation is a crucial post-translational modification characterized by covalent conjugation of small ubiquitin-like modifiers (SUMOs) to target proteins [4, 5], which exerts indispensable roles in various cellular processes, such as protein localization, gene transcription, and DNA replication [6,7,8]. The modification is a dynamic reversible process and the deconjugation of SUMOylation (deSUMOylation) is mediated by SUMO-specific proteases (SENPs) [9, 10]. Among the seven members of SENPs, SENP1 is wildly distributed in the nucleus and expressed in cytoplasm with functions of deconjugating a great number of SUMOylated proteins and processing the precursor SUMO to generate mature SUMO, which plays the most potent regulatory role in maintaining the balance of SUMOylation and deSUMOylation [11,12,13]. Little is known about the role of SENP1 in MCL
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