LncRNA16 inhibits pyroptosis and promotes platinum resistance in non-small cell lung cancer by sponging miRNA1827 to regulate MBD3/GSDME expression.

IF 6 2区医学 Q1 ONCOLOGY

Cancer Cell International Pub Date : 2025-05-24 DOI:10.1186/s12935-025-03812-z

Yanfang Liu, Yuanjun Zeng, Sikai Wang, Jiangyan Chen, Zhouqi Wang, Yang Zhao, Kuiyu Gong, Guihua Wang

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引用次数: 0

Abstract

Background: Platinum-based chemotherapy is the standard first-line cancer treatment. However, patients experience relapses due to chemoresistance. We found that long non-coding RNA 16 (lncRNA16) promotes platinum resistance and inhibits cell death in non-small cell lung cancer (NSCLC). However, the type of cell death inhibited by lncRNA16 remains unknown.

Methods: The biological roles of lncRNA16 and microRNA 1827 (miRNA1827) in cell proliferation and colony formation were determined using functional experiments. Dual-luciferase reporter and RNA immunoprecipitation assays were performed to confirm the interactions between lncRNA16 and miRNA1827. In vivo patient-derived tumor xenograft (PDX) models were used to investigate the effects of miRNA1827 agomir on platinum resistance.

Results: Pyroptosis was inhibited in platinum-resistant NSCLC cells. LncRNA16 contributed to the expression of methyl-CpG binding domain protein 3 (MBD3) by sponging miRNA1827, thereby inhibiting gasdermin E (GSDME) expression, which inhibited pyroptosis in platinum-resistant NSCLC. The miRNA1827 agomir repressed platinum resistance in vitro experiments and in vivo PDX models.

Conclusion: We identified a novel function of lncRNA16 in inhibiting pyroptosis and proposed an effective therapeutic drug, the miRNA1827 agomir, for chemosensitization. This study offers a potential strategy for treating patients with NSCLC, especially those with platinum resistance.

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LncRNA16通过海绵miRNA1827调控MBD3/GSDME的表达，抑制非小细胞肺癌的焦亡，促进铂耐药。

背景：以铂类药物为基础的化疗是标准的一线癌症治疗方案。然而，由于化疗耐药，患者会复发。我们发现长链非编码RNA16 （lncRNA16）在非小细胞肺癌（NSCLC）中促进铂耐药并抑制细胞死亡。然而，lncRNA16抑制细胞死亡的类型仍然未知。方法：通过功能实验确定lncRNA16和microRNA 1827 （miRNA1827）在细胞增殖和集落形成中的生物学作用。通过双荧光素酶报告基因和RNA免疫沉淀实验来证实lncRNA16和miRNA1827之间的相互作用。使用体内患者源性肿瘤异种移植（PDX）模型来研究miRNA1827 agomir对铂耐药的影响。结果：抗铂非小细胞肺癌细胞焦亡被抑制。LncRNA16通过海绵miRNA1827促进甲基- cpg结合域蛋白3 （MBD3）的表达，从而抑制gasdermin E （GSDME）的表达，从而抑制铂耐药NSCLC的焦亡。miRNA1827 agomir在体外实验和体内PDX模型中抑制铂耐药性。结论：我们发现了lncRNA16抑制焦亡的新功能，并提出了一种有效的治疗药物miRNA1827 agomir，用于化学增敏。这项研究为治疗非小细胞肺癌患者，特别是铂耐药患者提供了一种潜在的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.