Razipour Masoumeh, Jamali Zeinab, Sohrabpour Saeed, Heidari Farrokh, Lotfi Maryam, Ghadami Elham, Abtin Maryam, Maghsudlu Mohaddese, Sahebi Leyla, Shakoori Abbas
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
These two authors contributed equally to this work.
Mol Biol Res Commun. 2025;14(1):93-107. doi: 10.22099/mbrc.2024.50390.1996.
Long non-coding RNAs (lncRNAs) have recently emerged as critical regulators of oncogenic or tumor-suppressive pathways in human cancers. LINC01133 is a lncRNA that has exhibited dichotomous roles in various malignancies but to the best of our knowledge, the role of LINC01133 in laryngeal squamous cell carcinoma (LSCC) has not been previously investigated. This study aimed to investigate the expression, clinical significance, and potential functions of the LINC01133 in LSCC. Integrative bioinformatics analysis of sequencing data obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets revealed LINC01133 as a differentially expressed lncRNA in head and neck/laryngeal cancers. Experimental validation via quantitative real-time PCR in 41 pairs of stage III and IV LSCC tissues and normal tissues adjacent to the tumor (NAT) demonstrated significant downregulation of LINC01133 in tumors (<0.0001). Decreased LINC01133 expression associated with advanced tumor stage (=0.0206) and lymph node metastasis (=0.0203). The receiver operating characteristic analysis indicated potential diagnostic utility (AUC=0.7115, =0.001). Bioinformatic predictions and literature mining suggested two potential competing endogenous RNA (ceRNA) mechanisms whereby LINC01133 may act as a tumor suppressor by sponging miR-205-5p to derepress the leucine-rich repeat kinase 2 (LRRK2) and androgen receptor, leading to dysregulation of cancer-related signaling cascades. This study provides initial evidence that loss of lncRNA LINC01133 expression may promote LSCC tumorigenesis, possibly by dysregulating microRNA interactions. Further verification of its regulatory mechanisms and diagnostic value is warranted.
长链非编码RNA（lncRNAs）最近已成为人类癌症中致癌或肿瘤抑制途径的关键调节因子。LINC01133是一种lncRNA，在各种恶性肿瘤中表现出双重作用，但据我们所知，LINC01133在喉鳞状细胞癌（LSCC）中的作用此前尚未被研究。本研究旨在探讨LINC01133在LSCC中的表达、临床意义及潜在功能。对从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）数据集中获得的测序数据进行综合生物信息学分析，结果显示LINC01133是头颈/喉癌中差异表达的lncRNA。通过对41对III期和IV期LSCC组织及肿瘤旁正常组织（NAT）进行定量实时PCR实验验证，结果表明肿瘤中LINC01133显著下调（<0.0001）。LINC01133表达降低与肿瘤晚期（=0.0206）和淋巴结转移（=0.0203）相关。受试者工作特征分析表明其具有潜在的诊断效用（AUC=0.7115，=0.001）。生物信息学预测和文献挖掘提示了两种潜在的竞争性内源性RNA（ceRNA）机制，即LINC01133可能通过海绵吸附miR-205-5p来解除对富含亮氨酸重复激酶2（LRRK2）和雄激素受体的抑制，从而发挥肿瘤抑制作用，导致癌症相关信号级联失调。本研究提供了初步证据，表明lncRNA LINC01133表达缺失可能通过失调微小RNA相互作用促进LSCC肿瘤发生。有必要进一步验证其调控机制和诊断价值。
