中国癌症杂志2026，Vol.36Issue(4)：363-374,12.DOI:10.19401/j.cnki.1007-3639.2026.04.005
miR-107靶向NKD1对乳腺癌细胞线粒体氧化磷酸化影响的实验研究
Effect of miR-107 targeting NKD1 on mitochondrial oxidative phosphorylation in breast cancer cells
摘要
Abstract
Background and purpose:Mitochondrial oxidative phosphorylation is a key energy-generating pathway and is closely linked to aggressive biological behaviors in invasive cancers.Micro RNA(miRNAs)regulate tumor cell metabolic reprogramming and cellular functions through messenger RNA(mRNA)targeting.This study explored how microRNA-107(miR-107)modulates mitochondrial oxidative phosphorylation(OXPHOS)in breast cancer via targeting naked cuticle homolog 1(NKD1).Methods:NKD1 expression in breast cancer was first assessed by analyzing public databases(TNM)and its prognostic significance was evaluated.Additionally,breast cancer and adjacent normal tissue samples were retrospectively collected from patients who underwent surgical resection at the Department of Surgical Oncology,General Hospital of Ningxia Medical University between June 2024 and June 2025,following predefined inclusion and exclusion criteria.NKD1 expression in clinical tissues and breast cancer cell lines was validated by quantitative real-time PCR(qRT-PCR)and Western blot.We then constructed a stable NKD1-knockdown cell model.High-throughput RNA sequencing(RNA-seq)was performed to identify altered biological pathways upon NKD1 depletion.The regulatory effect of NKD1 on key proteins of the Wnt/β-catenin pathway and cellular oxidative phosphorylation were confirmed by Western blot.Weighted gene co-expression network analysis(WGCNA)identified core miRNA modules associated with breast cancer phenotypes from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Bioinformatics tools(TargetScan,miRWalk)was used to predict potential miRNAs high correlation with NKD1.Pan-cancer and survival analyses was used to reveal the expression and prognostic significance of miR-107.Dual-luciferase reporter assay was used to verify miR-107 directly targets NKD1.MDA-MB-231 cells were transiently transfected with miR-107 mimic,miR-107 inhibitor,or co-transfected with miR-107 inhibitor plus NKD1 siRNA,and oxidative phosphorylation levels were assessed by Western blot.This study was approved by the Ethics Committee of General Hospital of Ningxia Medical University(approval number:KYLL-2022-0514).Results:Bioinformatics database(TNM)combined with 10 paired tissue samples analysis revealed that NKD1 expression was downregulated in breast cancer,and its low expression was positively correlated with favorable patient prognosis.RNA-seq analysis further demonstrated that NKD1 knockdown significantly enriched pathways related to Wnt/β-catenin signaling and oxidative phosphorylation.Western blot results indicated that depleting NKD1 promoted Axin degradation,increased the protein levels of β-catenin and GSK-3β,and upregulated c-Myc and IDH2 expression.Treatment with the inhibitor IACS-010759 suppressed cell growth,and this inhibitory effect was partially reversed when combined with NKD1 knockdown(P<0.05).In addition,WGCNA analysis showed that the TCGA-ME brown and GEO-ME blue modules were highly associated with breast cancer phenotypes.Combining the above modules with database analysis shows,miR-107 was predicted as a potential upstream miRNA targeting NKD1 and NKD1 is negatively correlated with miR-107.Compared with normal tissues,elevated miR-107 expression in breast cancer correlated with poorer patient prognosis(P<0.05).Dual-luciferase reporter assays confirmed that NKD1 is a direct target of miR-107,and the expression of miR-107 is negatively correlated with NKD1.Moreover,compared with the siNKD1 group,oxidative phosphorylation levels were decreased in cells transfected with miR-107 inhibitor alone,but partially restored in cells co-transfected with miR-107 inhibitor and siNKD1(P<0.05).Conclusion:miR-107 promotes breast cancer malignant progression by targeting and inhibiting NKD1,thereby activating Wnt/β-catenin signaling and enhancing oxidative phosphorylation in breast cancer cells.关键词
氧化磷酸化/miR-107/NKD1/乳腺癌/Wnt/β-catenin信号转导通路Key words
Oxidative phosphorylation/miR-107/NKD1/Breast cancer/Wnt/β-catenin pathway分类
医药卫生引用本文复制引用
王嘉,刘丹,石斌,马小兰,肖雯..miR-107靶向NKD1对乳腺癌细胞线粒体氧化磷酸化影响的实验研究[J].中国癌症杂志,2026,36(4):363-374,12.基金项目
宁夏医科大学2023年校级科研项目(XM2022012),宁夏医科大学2025年校级科研项目(XY2025001),宁夏回族自治区自然科学基金(2026AAC030995). Ningxia Medical University 2023 University-Level Research Project(XM2022012),Ningxia Medical University 2025 University-Level Research Project(XY2025001),Ningxia Hui Autonomous Region Natural Science Foundation Project(2026AAC030995). （XM2022012）
