POSTN 通过调节 TNFAIP6 的表达促进 NSCLC 的进展。

IF 2.5 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical and biophysical research communications Pub Date : 2024-10-24 DOI:10.1016/j.bbrc.2024.150891
Nani Yang , Tianqing Yu , Beiyao Zheng , Wentao Sun , Yue Li , Wei Zhang , Yuanyuan Chen , Li Yuan , Xue Jun Wang , Junbin Wang , Fen Yang
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引用次数: 0

摘要

骨膜增生蛋白(POSTN)表达的异常上调与多种疾病相关的病理级联过程有关,特别是炎症反应、纤维化过程和肿瘤进展,包括非小细胞肺癌(NSCLC)。本研究旨在阐明 POSTN 在 NSCLC 中的功能作用和潜在机制。免疫组化和 Western 印迹分析一致显示,POSTN 在 NSCLC 组织和细胞系中的水平升高。POSTN的表达与患者的预后呈负相关。利用POSTN靶向siRNA进行的功能实验表明,POSTN能显著抑制NSCLC细胞的增殖、上皮细胞向间质转化(EMT)、迁移和侵袭,而通过质粒转染进行的POSTN过表达则增强了这些致癌特性。从机理上讲,RNA测序分析和随后的验证研究发现,POSTN能积极调节NSCLC中肿瘤坏死因子α诱导蛋白6(TNFAIP6)的转录表达。值得注意的是,POSTN和TNFAIP6的表达水平呈正相关,且它们的过表达与NSCLC的进展呈正相关。此外,TNFAIP6的过表达可挽救POSTN敲除对NSCLC恶性表型的抑制作用。总之,我们的研究结果表明,POSTN通过TNFAIP6的上调促进了NSCLC的恶性发展,使POSTN成为NSCLC预后和临床治疗策略的一个有前景的生物标志物和潜在治疗靶点。
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POSTN promotes the progression of NSCLC via regulating TNFAIP6 expression
Aberrant upregulation of Periostin (POSTN) expression has been implicated in various disease-related pathological cascades, notably inflammatory responses, fibrotic processes and tumor progression, including non-small cell lung cancer (NSCLC). The present study aimed to elucidate the functional role and underlying mechanisms of POSTN in NSCLC. Immunohistochemical and Western blot analysis consistently revealed elevated POSTN levels in NSCLC tissues and cell lines. POSTN expression negatively correlated with patient prognosis. Functional experiments utilizing POSTN-targeting siRNAs demonstrated a significant suppression of NSCLC cell proliferation, epithelial-to-mesenchymal transition (EMT), migration and invasion, whereas POSTN overexpression via plasmid transfection enhanced these oncogenic properties. Mechanistically, RNA sequencing analysis and subsequent validation studies revealed that POSTN positively modulates the transcriptional expression of tumor necrosis factor alpha-induced protein 6 (TNFAIP6) in NSCLC. Notably, a positive correlation was observed between POSTN and TNFAIP6 expression levels, and their overexpression positively correlated with NSCLC progression. Furthermore, TNFAIP6 overexpression rescued the inhibitory effects of POSTN knockdown on NSCLC malignant phenotypes. Collectively, our findings indicate that POSTN promotes NSCLC malignancy through TNFAIP6 upregulation, positioning POSTN as a promising biomarker and potential therapeutic target for NSCLC prognosis and treatment strategies in clinical settings.
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来源期刊
Biochemical and biophysical research communications
Biochemical and biophysical research communications 生物-生化与分子生物学
CiteScore
6.10
自引率
0.00%
发文量
1400
审稿时长
14 days
期刊介绍: Biochemical and Biophysical Research Communications is the premier international journal devoted to the very rapid dissemination of timely and significant experimental results in diverse fields of biological research. The development of the "Breakthroughs and Views" section brings the minireview format to the journal, and issues often contain collections of special interest manuscripts. BBRC is published weekly (52 issues/year).Research Areas now include: Biochemistry; biophysics; cell biology; developmental biology; immunology ; molecular biology; neurobiology; plant biology and proteomics
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