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山东大学学报 (医学版) ›› 2025, Vol. 63 ›› Issue (9): 108-115.doi: 10.6040/j.issn.1671-7554.0.2025.0357

• 临床医学 • 上一篇    下一篇

长链非编码RNA HEATR3反义RNA 1参与结直肠癌发生发展的功能及其临床意义

李梓绮1,魏闫若雪1,刘晓晗1,刘春铖1,赵然1,2,刘玉昆1,2   

  1. 1.山东大学齐鲁医学院, 山东 济南 250012;2.济宁医学院附属医院病理科, 山东 济宁 272029
  • 发布日期:2025-09-08
  • 通讯作者: 赵然. E-mail:zhaoran@mail.jnmc.edu.cn刘玉昆. E-mail:liuyukun@mail.jnmc.edu.cn
  • 基金资助:
    国家自然科学基金(81902815,81802786);山东省自然科学基金(ZR2023MH011,ZR2019BH044,ZR2018BH025)

The functional role and clinical significance of lncRNA HEATR3-AS1 in colorectal cancer tumorigenesis and progression

LI Ziqi1, WEI Yanruoxue1, LIU Xiaohan1, LIU Chuncheng1, ZHAO Ran1,2, LIU Yukun1,2   

  1. 1. Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. Department of Pathology, Affiliated Hospital of Jining Medical University, Jining 272029, Shandong, China
  • Published:2025-09-08

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摘要： 目的 探讨长链非编码RNA HEATR3反义RNA 1(lncRNA HEATR3 Antisense RNA 1, HEATR3-AS1)在结直肠癌(colorectal cancer, CRC)中的表达特征、亚细胞定位模式、分子功能、临床病理意义及预后评估价值。 方法 采用实时荧光定量PCR法检测结直肠癌组织中HEATR3-AS1的表达水平,荧光原位杂交技术明确其亚细胞定位,并分析HEATR3-AS1表达与HEATR3 mRNA表达水平的相关性。通过分子克隆技术构建HEATR3-AS1的真核表达载体,并构建其过表达细胞模型,从而明确其对HEATR3 mRNA表达的影响。采用原位杂交技术检测其在结直肠癌患者肿瘤组织中的表达,并探讨其表达与结直肠癌患者临床病理特征及不良生存预后的关联性。 结果 HEATR3-AS1在结直肠癌组织中的表达量较正常组织显著上调(P=0.019 2),且定位于结直肠癌细胞的细胞核。其表达水平与HEATR3 mRNA表达水平呈显著正相关(P=0.020 2),且其过表达促进HEATR3 mRNA的表达(P=0.007 7)。其高表达与TNM分期(P=0.029)及淋巴结转移(P=0.036)存在显著统计学关联。生存分析表明,相较于HEATR3-AS1低表达的结直肠癌患者群体,其高表达结直肠癌患者的总生存期(overall survival, OS)显著缩短(P=0.001 1)。多因素Cox分析显示,HEATR3-AS1高表达可作为结直肠癌患者独立的不良预后因素(HR=3.355,95%CI:1.632~7.193,P=0.001 3)。 结论 HEATR3-AS1在结直肠癌中表达上调且特异性定位于细胞核,其过表达可能参与HEATR3的转录调控过程,其异常高表达可作为评估结直肠癌患者预后的独立危险因素,有望成为结直肠癌分子分型和生存预测的新分子靶标。

关键词: 结直肠癌, 长链非编码RNA HEATR3-AS1, 原位杂交, 荧光原位杂交, 预后

Abstract: Objective To investigate the expression characteristics, subcellular localization, molecular functions, clinicopathological significance, and prognostic evaluation value of long non-coding RNA HEATR3-AS1 in colorectal cancer(CRC). Methods Quantitative real-time polymerase chain reaction(RT-qPCR)was used to detecte the expression level of HEATR3-AS1 in CRC tissues, and fluorescence in situ hybridization(FISH)was used to clarify its subcellular localization. The correlation between the expression of HEATR3-AS1 and HEATR3 mRNA was analyzed. The eukaryotic expression vector containing HEATR3-AS1 was constructed using molecular cloning techniques and the HEATR3-AS1-overexpressed cell model was constructed to elucidate the effect of its overexpression on HEATR3 mRNA expression. In situ hybridization(ISH)was employed to analyze the correlation of its expression in CRC tissues with clinicopathological features and poor prognosis in CRC patients. Results The expression of HEATR3-AS1 in CRC tissues demonstrated a marked upregulation compared with paracancerous normal tissues(P=0.019 2)and was explicitly localized in the nucleus of CRC cells. A significant positive correlation was observed between HEATR3-AS1 and HEATR3 mRNA expression levels(P=0.020 2), and its overexpression promoted the expression of HEATR3 mRNA(P=0.007 7). High expression of HEATR3-AS1 was significantly associated with advanced TNM stage(P=0.029)and lymph node metastasis(P=0.036). Survival curve analysis revealed that colorectal cancer patients with elevated HEATR3-AS1 expression experienced a marked reduction in overall survival(OS)compared to those with low expression(P=0.001 1). Multivariate Cox analysis confirmed that high expression of HEATR3-AS1 could serve as an independent poor prognostic factor in CRC patients(HR=3.355, 95%CI=1.632-7.193, P=0.001 3). Conclusion HEATR3-AS1 is overexpressed and specifically localized in the nucleus of CRC cells. Its overexpression may regulate the transcription of HEATR3, and its aberrantly high expression serves as an independent prognostic factor for colorectal cancer, highlighting its potential as a novel biomarker for molecular classification and survival prediction in CRC.

Key words: Colorectal cancer, lncRNA HEATR3 Antisense RNA 1, In situ hybridization, Fluorescence in situ hybridization, Prognosis

中图分类号: 

  • R735.3
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