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Title

SUMO-specific protease 1 exacerbates acute myeloid leukemia by enhancing beclin 1-dependent autophagy through polypyrimidine tract-binding protein 1 deSUMOylation.

Authors

Xing, Lina; Guo, Xuefei; Zhang, Xiaolei; Wang, Ying; Ren, Jinhai

Abstract

Genetic association between SUMO-specific protease 1 (SENP1) and acute myeloid leukemia (AML) has been validated. However, the mechanism by which SENP1 affects AML proliferation, apoptosis, and autophagy remains unknown. The levels of SENP1 and polypyrimidine tract-binding protein 1 (PTBP1) were measured in patients with AML, AML cell lines, and xenograft tissues. The effects of SENP1 on AML proliferation, apoptosis, and beclin 1 (BECN1)-dependent autophagy were assessed through in vitro and in vivo loss- or gain-of-function experiments. SUMOylation analysis using immunoprecipitation (IP), RNA pull-down, RNA IP (RIP), and RNA stability assays were used to explore the molecular mechanism of SENP1 in AML development. The SENP1 level was elevated in AML samples. Silencing SENP1 impeded the development of AML, as evidenced by the inhibition of proliferation and promotion of G1-phase arrest and apoptosis resulting from SENP1 depletion in AML cells. Moreover, silencing of SENP1 restrained BECN1-depentent autophagy in AML cells. In addition, the overexpression of BECN1 or PTBP1 partially neutralized the effect of SENP1 knockdown on AML cell behavior. Mechanistically, SENP1 mediated PTBP1 deSUMOylation, which then directly interacted with BECN1 mRNA and enhanced its stability. In vivo experiments further confirmed the repressive effects of SENP1 suppression on AML development. Collectively, the SENP1/PTBP1/BECN1 signaling axis has been identified as a significant therapeutic target for enhancing AML treatment.

Subjects

ACUTE myeloid leukemia; CELL lines; AUTOPHAGY; IMMUNOPRECIPITATION; APOPTOSIS

Publication

Journal of Leukocyte Biology, 2024, Vol 116, Issue 6, p1454

ISSN

0741-5400

Publication type

Academic Journal

DOI

10.1093/jleuko/qiae143

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