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

{"title":"LINC-PINT suppresses the progression of acute myeloid leukemia via miR-767-5p/SUZ12-mediated JAK/STAT signaling pathway","authors":"Lei Xiang , Xue Lin , Yong Wu","doi":"10.1016/j.cyto.2025.156883","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>The low expression of LINC-PINT was significantly related to ELN risk stratification (<em>p</em> = 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 (<em>r</em> = −0.3316, <em>p</em> = 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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156883"},"PeriodicalIF":3.7000,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytokine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1043466625000304","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

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.

Abstract Image

查看原文本刊更多论文

LINC-PINT通过miR-767-5p/ suz12介导的JAK/STAT信号通路抑制急性髓系白血病的进展

长链非编码RNA （lncRNA）长链基因间非蛋白编码RNA， p53诱导转录物（LINC-PINT）在癌细胞中显示出重要作用。然而，其在急性髓性白血病（AML）中的功能尚不清楚。方法采用实时荧光定量PCR检测AML患者中LINC-PINT和miR-767-5p的表达水平。通过RNA免疫沉淀（RIP）实验和荧光素酶报告基因实验验证miR-767-5p与LINC-PINT或zeste 12抑制因子（SUZ12）之间的相互作用。western blotting和免疫沉淀进一步证实了suz12介导的JAK/STAT信号通路。采用CCK-8和流式细胞术观察细胞增殖、细胞周期分布和凋亡情况。裸鼠体内模型检测肿瘤形成。结果LINC-PINT低表达与ELN危险分层有显著相关性（p = 0.028）。异位表达LINC-PINT抑制AML细胞株（THP-1和HL-60）的增殖和细胞周期G1/S转变，促进细胞凋亡。LINC-PINT过表达抑制肿瘤生长。LINC-PINT通过充当miR-767-5p的海绵正向调节SUZ12。AML患者miR-767-5p与LINC-PINT呈负相关（r = - 0.3316, p = 0.0336）。miR-767-5p的共表达逆转了LINC-PINT对AML细胞的影响。MiR-767-5p增强了AML的侵袭性，这被SUZ12的过表达所抵消。此外，SUZ12下调HDAC1以降低AML细胞中STAT3的磷酸化和乙酰化。总之，LINC-PINT通过miR-767-5p/ suz12介导的JAK/STAT信号通路在AML中发挥抑瘤作用，是AML的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

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.