首页|LINC00978在头颈鳞癌中的临床价值、生物学功能及潜在机制探讨

LINC00978在头颈鳞癌中的临床价值、生物学功能及潜在机制探讨

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目的 探讨长链非编码RNA(LncRNA)LINC00978在头颈鳞癌中的预后价值及其对FaDu细胞生长和凋亡的影响,并初步分析其潜在机制。方法 利用肿瘤综合数据库GEPIA和UALCAN分析LINC00978在头颈鳞癌组织及正常对照样本中的表达水平,以及LINC00978的表达和患者各临床参数之间的关系。采用实时荧光定量PCR(qRT-PCR)的方法检测LINC00978在头颈鳞癌细胞(FaDu、SCC4)和口腔黏膜细胞HOK中的相对表达水平。应用京都基因与基因组百科全书(KEGG)进行LINC00978的功能富集分析。分别采用CCK-8实验和流式细胞术检测FaDu细胞的生长和凋亡。应用RNA免疫共沉淀(RIP)证实LINC00978和METTL3蛋白的直接相互作用。采用Western blot检测沉默LINC00978后的FaDu细胞中METTL3蛋白水平变化。结果 与正常组织样本相比,LINC00978在头颈鳞癌组织样本中的表达水平明显升高(P<0。0001)。与HOK细胞相比,LINC00978在FaDu和SCC4中的表达水平显著上调(P<0。05)。高表达LINC00978与头颈鳞癌患者的肿瘤分期、分级、年龄、性别、总生存及无疾病生存显著相关。KEGG富集分析结果显示,LINC00978在头颈鳞癌中可能主要参与代谢、DNA复制、凋亡等生物学途径。与转染阴性对照siRNA(si-NC)相比,转染靶向LINC00978的siRNA(si-LINC00978#1、si-LINC00978#2)均可以明显抑制FaDu细胞的生长(P<0。05)并促进细胞凋亡(P<0。05)。LINC00978和MEITL3蛋白在FaDu细胞中存在直接相互作用。沉默LINC00978引起FaDu细胞中METTL3蛋白水平降低。过表达METTL3可以明显挽救敲低LINC00978对FaDu细胞增殖的抑制作用。结论 LINC00978作为促癌分子在头颈鳞癌中表达上调并且是患者生存较差的预后指标,LINC00978可能通过结合并调节METTL3维持头颈鳞癌细胞的存活。
Clinical value,biological function and potential mechanism of LINC00978 in head and neck squamous cell carcinoma
Objective To investigate the prognostic value of long non-coding RNA(LncRNA)LINC00978 in head and neck squamous cell carcinoma(HNSCC)and its effects on the growth and apoptosis of FaDu cells,and to analyzed its po-tential mechanism.Methods Cancer databases GEPIA and UALCAN were used to analyze the expression level of LINC00978 in HNSCC samples and normal samples,and the relationship between the LINC00978 expression and clinical parameters of patients.The relative expression levels of LINC00978 in human HNSCC cell lines(FaDu,SCC4)and one oral mucosa cell line(HOK)were detected by quantitative real-time fluorescence PCR(qRT-PCR).Functional en-richment analysis of LINC00978 was performed based on the Kyoto Encyclopedia of Genes and Genomes(KEGG).The growth and apoptosis of FaDu cells were detected by CCK-8 assay and flow cytometry,respectively.Direct interaction be-tween LINC00978 and METTL3 protein was confirmed by RNA immunoprecipitation(RIP).Western blot was used to de-tect the changes of METTL3 protein in FaDu cells after LINC00978 silence.Results Compared with normal tissue sam-ples,the expression level of LINC00978 in HNSCC tissue samples was significantly increased(P<0.0001).Compared with HOK cells,the expression levels of LINC00978 in FaDu and SCC4 were significantly up-regulated(P<0.05).High expression of LINC00978 was significantly correlated with tumor stage,grade,age,gender,overall survival and dis-ease-free survival in patients with HNSCC.KEGG enrichment analysis indicated that LINC00978 may be involved in me-tabolism,DNA replication,apoptosis and other biological pathways in HNSCC.Compared with negative control siRNA(si-NC),silencing of LINC00978(si-LINC00978#1 and si-LINC00978#2)could significantly inhibit the growth of FaDu cells(P<0.05)and promote cell apoptosis(P<0.05).LINC00978 and METTL3 protein have direct interaction in FaDu cells.Silencing of LINC00978 resulted in decreased METTL3 protein levels in FaDu cells.Over-expression of METTL3 can obviously save the inhibitory effect of LINC00978 knockdown on the proliferation of FaDu cells.Conclusion The expression of LINC00978 as a cancer promoting molecule is up-regulated in HNSCC,and is a prognos-tic indicator of poor survival.LINC00978 may maintain the survival of HNSCC by binding and regulating METTL3.

LINC00978Head and neck squamous cell carcinomaPrognosisCell proliferationMETTL3

赵春红、李玉杰、韩伟、于敏

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郑州大学附属郑州中心医院耳鼻咽喉头颈外科,郑州 450007

LINC00978 头颈鳞癌 预后 细胞增殖 METTL3

2024

医药论坛杂志
中华预防医学会,河南省医学情报研究所

医药论坛杂志

影响因子:0.47
ISSN:1672-3422
年,卷(期):2024.45(3)
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