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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

32卷

期数:

2026年02期

页码:

117-125

栏目:

肿瘤疾病专题

出版日期:

2026-03-20

文章信息/Info

Title:

LINC01296 modulates STAT3 to affect cisplatin sensitivity in head and neck squamous cell carcinoma

文章编号:

1006-8147(2026)02-0117-09

作者:

刘小龙¹; 王聿凊¹; 郑建伟¹; 孙孟宇³; 周旋³; 任玉²; 梅玫¹

（1.天津医科大学基础医学院细胞生物学系，天津 300070；2.天津医科大学基础医学院遗传学系，天津300070；3.天津医科大学肿瘤医院颌面耳鼻喉肿瘤科，天津300060）

Author(s):

LIU Xiaolong¹;  WANG Yuqing¹;  ZHENG Jianwei¹;  SUN Mengyu³;  ZHOU Xuan³;  REN Yu²;  MEI Mei¹

（1. Department of Cell Biology， School of Basic Medical Sciences， Tianjin Medical University， Tianjin 300070， China； 2. Department of Genetics， School of Basic Medical Sciences， Tianjin Medical University， Tianjin 300070， China； 3. Department of Maxillofacial and Otorhinolaryngology Oncology， Tianjin Medical University Cancer Institute and Hospital， Tianjin 300060， China）

关键词:

LINC01296; 头颈部鳞状细胞癌; 信号转导及转录激活因子3; 顺铂

Keywords:

LINC01296;  head and neck squamous cell carcinoma;  signal transducer and activator of transcription 3;  cisplatin

分类号:

R739.91

DOI:

10.20135/j.issn.1006-8147.2026.02.0117

文献标志码:

A

摘要:

目的：探究LINC01296在头颈部鳞状细胞癌（HNSCC）中表达与临床相关性及其对顺铂敏感性的影响。方法：通过癌症基因组图谱（TCGA）数据库分析LINC01296在HNSCC中的表达及预后。实时荧光定量聚合酶链反应（RT-qPCR）与荧光原位杂交（FISH）检测HNSCC患者的肿瘤、癌旁组织中LINC01296表达差异，并收集患者的临床病理资料。RT-qPCR检测HNSCC各空白组细胞中LINC01296的表达水平。细胞增殖检测实验、平板克隆实验和流式细胞术检测shNC组和shLINC01296组的细胞增殖和凋亡。通过核糖核酸-蛋白质结合预测、核糖核酸沉降与核糖核酸免疫沉淀实验验证LINC01296与信号转导及转录激活因子3（STAT3）的相互作用。RT-qPCR和蛋白印迹法实验检测shNC和shLINC01296组细胞STAT3 mRNA和蛋白水平。实验设置敲低对照组（shNC）、敲低LINC01296组（shLINC01296）、过表达对照组（Vector）、过表达STAT3组（STAT3）、敲低LINC01296并过表达STAT3组（shLINC01296+STAT3）。分别通过蛋白印迹法、细胞增殖检测实验和平板克隆实验检测敲低LINC01296对SCC15细胞顺铂敏感性的影响。免疫组化（IHC）评估肿瘤组织中p-STAT3Y705与LINC01296的相关性。结果：TCGA结果显示，LINC01296在HNSCC肿瘤组织中高表达（t=6.711，P<0.001），并与预后不良相关（HR=1.42，95%CI：1.09～1.85，P=0.01）。RT-qPCR结果显示LINC01296在患者肿瘤组织中高表达（t=3.641，P<0.001）。FISH染色显示，LINC01296在患者肿瘤组织中显著高表达。临床特征显示LINC01296表达与T分期（χ2=13.463 4，P<0.001）和AJCC分期（χ2=4.958 3，P<0.05）呈正相关。在SCC15细胞中，LINC01296的表达相对较高。与shNC组相比，敲低LINC01296降低细胞增殖速率（t=5.135，P<0.001）和克隆形成数量（t=18.00，P＜0.000 1），同时促进细胞凋亡（t=5.861，P<0.01）。LINC01296与STAT3蛋白直接结合；敲低LINC01296后，STAT3 mRNA和蛋白水平无明显变化（均P>0.05），STAT3Y705的磷酸化水平降低，SCC15细胞对顺铂的敏感性恢复。IHC结果显示，p-STAT3Y705与LINC01296的表达呈正相关（r=0.61，P<0.001）。结论：LINC01296在HNSCC中高表达并与预后不良相关，通过调控STAT3磷酸化可降低HNSCC细胞对顺铂的敏感性。

Abstract:

Objective： To investigate the expression and clinical relevance of LINC01296 in head and neck squamous cell carcinoma （HNSCC） and its effect on cisplatin sensitivity. Methods： The Cancer Genome Atlas（TCGA） database analysis evaluated LINC01296 expression and prognosis in HNSCC. Real-time fluorescent quantitative polymerase chain reaction（RT-qPCR） and fluorescence in situ hybridization（FISH） were used to quantify the differential expression of LINC01296 in tumor and adjacent non-tumor tissues from HNSCC patients， and clinicopathological data were compiled. The expression level of LINC01296 in control cells of HNSCC was detected by RT-qPCR. Cell proliferation assay， colony formation assay and flow cytometry were used to detect cell proliferation and apoptosis in the shNC group and shLINC01296 group. The interaction between LINC01296 and signal transducer and activator of transcription 3 （STAT3） was predicted by RNA-protein interaction prediction using only sequence information（RPISeq） and verified through RNA pull-down and RNA immunoprecipitation（RIP） assays. RT-qPCR and Western blotting were used to quantify STAT3 mRNA and protein levels in the shNC group and LINC01296 knockdown group. Groups including shNC， shLINC01296， Vetocr， STAT3， and shLINC01296+STAT3 were established， and the effect of LINC01296 knockdown on cisplatin sensitivity in SCC15 cells was evaluated by Western blotting， cell proliferation assays， and colony-formation assays. Immunohistochemistry （IHC） was used to evaluate the correlation between p-STAT3Y705 and LINC01296 in tumor tissues. Results： TCGA data showed that LINC01296 was highly expressed in HNSCC tumor tissues （t=6.711，P<0.001） and associated with poor prognosis（HR=1.42， 95% CI： 1.09-1.85， P=0.01）. RT-qPCR results demonstrated that LINC01296 was highly expressed in tumor tissues（t=3.641，P<0.001）. FISH staining demonstrated markedly higher LINC01296 expression in tumor tissues. Clinical characteristics analysis indicated that LINC01296 expression positively correlated with T stage （χ2=13.463 4，P<0.001） and AJCC stage （χ2=4.958 3，P<0.05）. In SCC15 cells， LINC01296 expression was relatively high. Compared with the knockdown control group， knockdown of LINC01296 decreased the cell proliferation rate （t=5.135，P<0.001） and colony formation number（t=18.00，P＜0.000 1）， while promoting cell apoptosis （t=5.861，P<0.01）. Knockdown of LINC01296， which directly binds to STAT3， specifically reduced STAT3Y705 phosphorylation without altering STAT3 mRNA or protein levels， and restored DDP sensitivity in SCC15 cells. IHC analysis revealed a statistically significant positive correlation between p-STAT3Y705 and LINC01296 expression（r=0.61， P<0.001）. Conclusion： LINC01296 is highly expressed and associated with poor prognosis in HNSCC， which reduces cisplatin sensitivity in HNSCC cells by regulating STAT3 phosphorylation.

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备注/Memo

备注/Memo:

基金项目 国家自然科学基金面上项目（82272663）
作者简介 刘小龙（1997-），男，硕士在读，研究方向：细胞生物学；通信作者：梅玫，E-mail：meim@tmu.edu.cn。

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更新日期/Last Update: 2026-03-20