ABERRANT METHYLATION-MEDIATED DOWNREGULATION OF THE LINC01554 GENE ACCELERATES THE MALIGNANT PROGRESSION AND REGULATES THE CHEMOSENSITIVITY OF LARYNGEAL SQUAMOUS CELL CARCINOMA

Laryngeal squamous cell carcinoma (LSCC) is diagnosed as a malignant tumor with a poor prognosis, the associated mechanisms still need to be further investigated. The LINC01554 gene is confirmed to participate in the tumorigenesis of hepatocellular carcinoma, but its role in LSCC has not been investigated. The aim of this study was to investigate the function and the potential mechanism of LINC01554 in LSCC, LINC01554 further was used as a molecular target for the diagnosis and molecular targeted therapy of LSCC. The microarray-based gene expression profiling of LSCC and its adjacent non-tumor tissue were used to identify the differentially expressed long non-coding RNAs (lncRNAs). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to verify the expression levels of LINC01554 in tissue and LSCC cell lines. The DNA methylation level of the LINC01554 promoter was detected by the application of bisulfite genomic sequencing ( BGS), and the bisulfite conversion- specific/ methylation-specific polymerase chain reaction (BS-MSP) method. The effect of LINC01554 on the proliferation, migration, and invasion of squamous cell carcinoma was assessed by MTS, wound healing, transwell, RT-qPCR, Western blot in vitro-cultured TU177 cells, and AMC-HN-8 cells. The microarray-based gene expression profiling identified the differentially expressed lncRNAs, including LINC01554, with downregulation in the LSCC tissue vs. normal tissue. The RT-qPCR verified the downregulation of LINC01554 in the LSCC tissue (P=0.0049) and LSCC cell (P=0.0020). The BGS and BS-MSP exhibited the hypermethylation level of the LINC01554 promoter, which mediated the downregulation of LINC01554. A gain-of-function experiment showed that LINC01554 inhibited the proliferation, migration, and invasion of TU177 and AMC-HN-8. Subsequently, LINC01554 overexpression was shown to decrease cell viability in TU177 and AMC-HN-8 cells treated with cisplatin. Our findings indicated that the aberrant methylation-mediated downregulation of LINC01554 promoted malignant progression and cisplatin resistance in LSCC, and LINC01554 may serve as a potential diagnostic biomarker and a novel therapeutic target for LSCC.