m6A Modification-Mediated LINC01547 Promotes Pancreatic Cancer Growth and Gemcitabine Resistance Through miR-34a-5p/MYH9 Axis.

IF 1.6 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical Genetics Pub Date : 2025-10-05 DOI:10.1007/s10528-025-11254-5

Guangrui Lu, Jianhua Gong, Yue Chen, Xiaosong Li, Junyi Wang, Jun Hu

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引用次数: 0

Abstract

Gemcitabine (GEM) resistance undermines chemotherapy efficacy for pancreatic ductal adenocarcinoma (PDAC), resulting in poor prognosis. Long non-coding RNAs (LncRNAs) participate in various malignant tumors, including PDAC. However, their roles in GEM resistance require further elucidation. Here, we investigated the function of LINC01547 in PDAC progression and chemoresistance. LINC01547 was significantly upregulated in PDAC tissues and cell lines, and its high expression correlated with unfavorable patient outcomes. Silencing LINC01547 dramatically suppressed cellular proliferation, sphere formation capability and enhanced GEM sensitivity of PDAC cells both in vitro and in vivo experiments. Mechanistically, LINC01547 as a competing endogenous RNA that could regulate miR-34a-5p. RNA-sequencing and luciferase reporter analysis demonstrated that miR-34a-5p directly targets MYH9. Additionally, METTL3 mediated m6A modification boosted the RNA stabilization and upregulation of LINC01547. Taken together, these findings indicate that LINC01547 could promote tumor progression and gemcitabine resistance in PDAC via miR-34a-5p/MYH9 axis, highlighting LINC01547 as a potential biomarker and therapeutic target for overcoming chemoresistance in PDAC.

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m6A修饰介导的LINC01547通过miR-34a-5p/MYH9轴促进胰腺癌生长和吉西他滨耐药

吉西他滨（GEM）耐药破坏了胰腺导管腺癌（PDAC）的化疗效果，导致预后不良。长链非编码rna （LncRNAs）参与多种恶性肿瘤，包括PDAC。然而，它们在GEM耐药中的作用有待进一步阐明。在这里，我们研究了LINC01547在PDAC进展和化疗耐药中的功能。LINC01547在PDAC组织和细胞系中显著上调，其高表达与患者预后不良相关。在体外和体内实验中，沉默LINC01547可显著抑制PDAC细胞的增殖、成球能力和增强GEM敏感性。在机制上，LINC01547作为一种竞争的内源性RNA可以调节miR-34a-5p。rna测序和荧光素酶报告基因分析表明，miR-34a-5p直接靶向MYH9。此外，METTL3介导的m6A修饰促进了LINC01547的RNA稳定和上调。综上所述，这些发现表明，LINC01547可以通过miR-34a-5p/MYH9轴促进PDAC的肿瘤进展和吉西他滨耐药，突出了LINC01547作为克服PDAC化疗耐药的潜在生物标志物和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochemical Genetics 生物-生化与分子生物学

CiteScore

3.90

自引率

0.00%

发文量

133

审稿时长

4.8 months

期刊介绍： Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.