NKILA-miR-889-3p轴在调控口腔鳞状细胞癌细胞增殖迁移与侵袭中的作用OACSTPCD
Role of the NKILA-miR-889-3p Axis in Regulating Proliferation Migration and Invasion of Oral Squamous Cell Carcinoma Cells
目的:通过分析长非编码 RNA NKILA 在口腔鳞状细胞癌(OSCC)中的表达及其临床意义,探讨NKILA与其潜在靶向miRNA之间的交互调控机制,以阐明其在OSCC发展中的作用.方法:收集了80 例经病理学证实的OSCC患者及相应邻近正常口腔黏膜组织样本,使用 qRT-PCR 检测 NKILA的表达水平及其与预后.利用克隆形成实验和Transwell迁移侵袭实验评估NKILA对OSCC细胞增殖、迁移和侵袭的影响.通过亚细胞分离实验确定NKILA的亚细胞定位,并使用LncBase预测NKILA的潜在靶miRNA.AGO2 免疫沉淀实验用于验证miR-889-3p 与 NKILA 的交互作用.结果:与相应的正常组织相比,NKILA在OSCC组织中的表达显著降低(P＜0.0001),且其低表达与 OSCC 患者的晚期 TNM分期、淋巴结转移和远处转移显著相关(P=0.001,P=0.046,P=0.011).细胞实验结果表明,NKILA的敲低显著促进了OSCC细胞的迁移和侵袭能力(P＜0.05),而 NKILA 的过表达则显著抑制了这些细胞功能(P＜0.05).亚细胞定位实验显示NKILA主要位于细胞质.miR-889-3p 被识别为NKILA的潜在靶点,过表达NKILA可显著上调miR-889-3p 的表达(P＜0.05),反之亦然.AGO2 免疫沉淀实验进一步证实了miR-889-3p能特异性结合并调节NKILA(P＜0.05).结论:本研究明确了NKILA在OSCC发展中的下调现象及其潜在的功能机制,揭示了 NKILA 与 miR-889-3p 之间的重要交互调控关系,为OSCC的研究和治疗提供了新的见解.
Objective:To analyze the expression and clinical significance of the long non-coding RNA NKILA in oral squamous cell carcinoma(OSCC),investigate the regulatory mechanism between NKILA and its potential target miRNA,and elucidate its role in OSCC development.Methods:Eighty OSCC patients con-firmed by pathology and corresponding adjacent normal oral mucosa tissue samples were collected.The expres-sion level of NKILA and its correlation with prognosis were detected using qRT-PCR.The effects of NKILA on OSCC cell proliferation,migration,and invasion were evaluated through colony formation assays and Transwell assays.Subcellular fractionation experiments were conducted to determine the subcellular localization of NKI-LA.LncBase was used to predict potential target miRNAs of NKILA.AGO2 immunoprecipitation experiments were performed to validate the interaction between miR-889-3p and NKILA.Results:NKILA expression was significantly downregulated in OSCC tissues compared to adjacent normal tissues(P＜0.0001).Low expres-sion of NKILA was significantly associated with advanced TNM stage,lymph node metastasis,and distant me-tastasis in OSCC patients(P=0.001,P=0.046,P=0.011).Cell experiments demonstrated that knockdown of NKILA significantly promoted OSCC cell migration and invasion(P＜0.05),while overexpression of NKILA significantly inhibited these cellular functions(P＜0.05).Subcellular localization experiments showed that NKILA primarily localized in the cytoplasm.miR-889-3p was identified as a potential target of NKILA,and overexpression of NKILA significantly upregulated miR-889-3p expression(P＜0.05),and vice versa.AGO2 immunoprecipitation experiments further confirmed that miR-889-3p specifically binds to and regulates NKILA(P＜0.05).Conclusion:This study elucidates the downregulation of NKILA in OSCC development and its potential functional mechanisms.It reveals an important regulatory interaction between NKILA and miR-889-3p,providing new insights for the study and treatment of OSCC.
杨硕;王妍心;仇永乐;李昆珊;吴倩
河北省石家庄市人民医院口腔科,河北 石家庄 050000河北医科大学第四医院口腔科,河北 石家庄 050000河北大学附属医院口腔科,河北 保定 071000
口腔鳞状细胞癌长非编码RNA NKILAmiRNA侵袭增殖迁移
Oral squamous cell carcinomaLong non-coding RNA NKILAmiRNAInvasionProliferationMigration
《河北医学》 2024 (008)
1233-1238 / 6
河北省医学科学研究重点课题计划,(编号:20230885)
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