No abstract

MicroRNAs (miRNAs) are known to play a regulatory role in various cancers including laryngocarcinoma. MiR‐29a‐3p is a potential tumor‐suppressive miRNA, but its function in laryngocarcinoma is unknown. The purpose of this study was to investigate the roles of miR‐29a‐3p in laryngocarcinoma. Prominin1 (PROM1) was predicted as a target gene of miR‐29a‐3p and this was verified using a luciferase reporter assay. Transfection of miR‐29a‐3p into two laryngocarcinoma cell lines indicated that miR‐29a‐3p could decrease cell proliferation and enhance the chemotherapy response by targeting PROM1. PROM1 expression was up‐regulated in the laryngocarcinoma cells when miR‐29a‐3p was down‐regulated. We found miR‐29a‐3p expression levels were lower in laryngocarcinoma tissues than in control tissues. We also found that miR‐29a‐3p expression was negatively correlated with PROM1 expression in laryngocarcinoma tissues. The study demonstrates that miR‐29a‐3p suppresses cell proliferation in laryngocarcinoma by targeting PROM1.

Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer and accounts for 1% to 2% of all malignancies diagnosed worldwide. Runt-related transcription factor 3 (RUNX3), an important tumor suppressor, is known to related to lymph node metastasis and the development of LSCC. However, the biological roles and potential mechanisms RUNX3 expression was not well understood. In this study, we reported that the RUNX3 was significantly downregulated and highly methylated in LSCC compared with their matched normal. The enforced expression of RUNX3 inhibited LSCC cell migration, invasion, and proliferation, whereas the inhibition of RUNX3 did the opposite. We identified that RUNX3 was regulated by miR-148a-3p and found that the expression level of miR-148-3p was significantly decreased and positively related with the expression of RUNX3 in LSCC. We also identified that DNA methyltransferase enzyme DNA (cytosine-5-)-methyltransferase 1 (DNMT1) was targeted by miR-148a-3p in LSCC. The knockdown of DNMT1 promoted the expression of RUNX3 and inhibited migration, invasion, and proliferation in LSCC cells. In summary, our study demonstrated that miR-148a-3p may regulate RUNX3 expression through the modulation of DNMT1-dependent DNA methylation in LSCC, providing a novel target and a potential therapeutic pathway against LSCC. LSCC is a highly aggressive malignant cancer and accounts for 1% to 2% of all malignancies diagnosed worldwide. In this study, we reported that RUNX3, an important tumor suppressor, was significantly downregulated and highly methylated in LSCC compared with their matched normal. The overexpression of RUNX3 inhibited LSCC cell migration, invasion, and proliferation, whereas the inhibition of RUNX3 did the opposite. Moreover, RUNX3 was regulated by miR-148a-3p, which targeted DNA methyltransferase enzyme DNMT1 in LSCC cells. Therefore, miR-148a-3p may regulate RUNX3 expression through the modulation of DNMT1-dependent DNA methylation in LSCC, providing a novel target and a potential therapeutic pathway against LSCC.

No abstract

A total of 725 DEGs were identified from the training set. A total of 4126 gene pairs showed significant correlations in non-recurred LC only, corresponding to 533 genes. A total of 7235 gene pairs showed significant correlations in recurred LC only, corresponding to 608 genes. Besides, 1694 gene pairs showed significant correlations in both non-recurred and recurred LC, corresponding to 322 genes. Functional enrichment analysis was performed for the three groups of DEGs. Seven overlapping biological functions were revealed: positive regulation of chondrocyte differentiation, autoimmune thyroid disease, focal adhesion, linoleic acid metabolism, drug metabolism, organic cation transport, and ECM-receptor interaction. Eight feature genes (PDIA3, MYH11, PDK1, SDC3, RPE65, LAMC3, BTK, and UPK1B) were identified. Their prognostic effect was validated by independent test set as well as survival analysis.