LINC-PINT suppresses the progression of acute myeloid leukemia via miR-767-5p/SUZ12-mediated JAK/STAT signaling pathway

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Cytokine Pub Date : 2025-02-19 DOI:10.1016/j.cyto.2025.156883

Lei Xiang , Xue Lin , Yong Wu

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引用次数: 0

Abstract

Background

Long noncoding RNA (lncRNA) long intergenic non-protein-coding RNA, p53-induced transcript (LINC-PINT) has shown a crucial role in cancer cells. However, its function in acute myeloid leukemia (AML) is unclear.

Methods

The expression levels of LINC-PINT and miR-767-5p in AML patients were measured through quantitative real-time PCR. The interaction between miR-767-5p and LINC-PINT or suppressor of zeste 12 (SUZ12) was verified by RNA immunoprecipitation (RIP) assay and luciferase reporter assay. SUZ12-mediated JAK/STAT signaling pathway was further confirmed using western blotting and immunoprecipitation. Cell proliferation, cell cycle distribution, and apoptosis were evaluated by CCK-8 and flow cytometry. Tumor formation was examined by a nude mice model in vivo.

Results

The low expression of LINC-PINT was significantly related to ELN risk stratification (p = 0.028). Ectopic expression of LINC-PINT restrained the proliferation and cell cycle G1/S transition and promoted apoptosis in AML cell lines (THP-1 and HL-60). LINC-PINT overexpression curbed tumor growth. LINC-PINT positively regulated SUZ12 by functioning as a sponge of miR-767-5p. There was a negative correlation between miR-767-5p and LINC-PINT in AML (r = −0.3316, p = 0.0336). Co-expression of miR-767-5p reversed the impacts of LINC-PINT on AML cells. MiR-767-5p enhanced the aggressiveness of AML, which was counteracted by overexpression of SUZ12. Additionally, SUZ12 downregulated HDAC1 to reduce STAT3 phosphorylation and acetylation in AML cells.

Conclusions

Overall, LINC-PINT serves as a tumor suppressor in AML through the miR-767-5p/SUZ12-mediated JAK/STAT signaling pathway, presenting a potential therapeutic target for AML.

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.