miR-34c-5p mediates the cellular malignant behaviors of oral squamous cell carcinoma through targeted binding of TRIM29.

BACKGROUND: This investigation examined the effects of the microRNA miR-34c-5p on the proliferation, migration, and invasion of oral squamous cell carcinoma (OSCC) and the mechanisms involved. METHODS: The Gene Expression Omnibus (GEO) database was used to filter the chips, and the GEO2R software (https://www.ncbi.nlm.nih.gov/geo/geo2r/) was used to analyze the microarray data (GSE28100 and GSE45238). Gene set enrichment analysis (GSEA) was used to study the relationship between the expression of miR-34c-5p and the distant metastasis and pathological grade of OSCC. The correlation between TRIM29 (tripartite motif containing 29) expression and the malignant clinical phenotype of OSCC was also examined. The mRNA and protein expression levels of miR-34c-5p and TRIM29 were measured by real time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot analysis. The proliferation, migration, invasion and apoptosis of the human oral squamous carcinoma cell lines CAL-27 and Tca8113 was assessed by performing cell-counting kit-8 (CCK-8) assays, colony formation assays, transwell tests, wound scratch tests and flow cytometry. Luciferase reporter assays were used to predict the relationship between miR-34c-5p and TRIM29. A xenograft nude model was established and used to evaluate the effect of miR-34c-5p on tumor growth in female BALB/c mice. RESULTS: The expression of miR-34c-5p was significantly correlated with the proliferation, migration, and metastasis of OSCC. Overexpression of miR-34c-5p promoted the proliferation, migration, and invasion of CAL-27 and Tca8113 cells, and suppressed their apoptosis. Inversely, low expression of miR-34c-5p suppressed the proliferation, migration, and invasion of CAL-27 and Tca8113 cells, and promoted their apoptosis. Overexpression of miR-34c-5p promoted tumor growth in the xenograft nude mice model. The expression of TRIM29 was related to malignant clinical phenotype of OSCC. Overexpression of TRIM29 inhibited the proliferation, migration and invasion of CAL-27 and Tca8113 cell, and induced their apoptosis. TRIM29 knockout had just the opposite effect. Importantly, miR-34c-5p binds to TRIM29 and inhibited TRIM29 expression. CONCLUSIONS: MiR-34c-5p regulates the proliferation, migration, invasion, and apoptosis of OSCC through targeted binding of TRIM29. This may represent a novel therapeutic target for the treatment of patients with OSCC.

miR-129-5p in exosomes inhibits diabetes-associated osteogenesis in the jaw via targeting FZD4.

Diabetes mellitus (DM) influence induces poor osseointegration. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is a critical factor in successful dental implants. Certain microRNAs play important roles during bone development, and others are deregulated in diabetes. This study investigated the roles of miR-129-5p in the osteoblast differentiation regulation. Exosomes containing miR-129-5p inhibited the osteoblast differentiation and was found in the blood of DM rats. The BMSCs isolated from the jaw of rats were used to detect the miR-129-5p expression. Frizzled (FZD) proteins function as receptors for WNT ligands. The FZD4 was the target of miR-129-5p in dual luciferase assay and Western blot. The miR-129-5p inhibited osteoblast differentiation and decreased the osteoblast markers. The exosomes isolated from the blood of DM rats showed more miR-129-5p level. Results suggested that the exosomes containing miR-129-5p maybe regulators of BMSCs in jaw. The collected exosomes containing miR-129-5p showed the inhibition effect in osteoblast differentiation and decreased the expression osteoblastic markers by targeting FZD4/ß-catenin signaling pathway. Therefore, the exosomes containing miR-129-5p in DM rats inhibits osteoblast differentiation by targeting FZD4/ß-catenin pathway.

NUDT1: A potential independent predictor for the prognosis of patients with oral squamous cell carcinoma.

OBJECTIVE: The current study was aimed to investigate the association of nudix hydrolase 1 (NUDT1) levels with the prognosis of oral squamous cell carcinoma (OSCC) patients. MATERIAL AND METHODS: Western immunoblotting and qRT-PCR were used to detect the protein and mRNA levels of NUDT1 in 31 cases of OSCC and normal tissues. The paraffin-embedded 62 cases of OSCC and 18 normal tissues were collected, and the pathological alterations were assessed by immunohistochemistry. The prognosis of all patients was followed up. Kaplan-Meier method was used to analyze the survival rate, and Cox regression was used for multivariate analysis. RESULTS: Both the protein and gene levels of NUDT1 were statistically increased (P = .0007 and P < .0001) in the OSCC tissue and had a significant association with the histopathologic grades of OSCC (P < .0001 and P = .0223). Immunohistochemistry detection of NUDT1 in 62 human OSCC tissues and 18 normal control tissues showed that NUDT1 expression was significantly increased in OSCC tissue and showed a strong association with histopathologic grades (P < .0001) and tumor stage (P = .005). Patients with high NUDT1 expression exhibited poorer overall survival rate (OS) and tumor-specific survival rate (TSS) than those with low NUDT1 expression (P < .0001 and P = .0008), and NUDT1 was independent prognostic factors for OS and TSS (P < .0001 and P < .001). CONCLUSION: The expression level of NUDT1 might be used to predict the prognosis of OSCC patients.