Dysregulated LINC01133 expression in laryngeal carcinoma: Prognostic implications and predicted ceRNA interactome

Document Type : Original article

Authors

1 Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Otorhinolaryngology Research Center, AmirAlam Hospital, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Pathology and Otorhinolaryngology Research Center, AmirAlam Hospital, Tehran University of Medical Sciences, Tehran, Iran

4 Family Health Research Institute, Maternal-Fetal and Neonatal Research Center, Tehran University of Medical Sciences, Tehran, Iran

5 Department of Medical Genetics, Cancer Institute of Iran, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

Abstract

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 (p<0.0001). Decreased LINC01133 expression associated with advanced tumor stage (p=0.0206) and lymph node metastasis (p=0.0203). The receiver operating characteristic analysis indicated potential diagnostic utility (AUC=0.7115, p=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.

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