[Relationships between microRNA expressions and prognosis in patients with tongue squamous cell carcinoma and the mechanisms microRNA regulating tongue squamous cell carcinoma biological behavior].

Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is well known for its high rate of proliferation and lymph nodal metastasis. Exploring the underlying pathways regulating TSCC could provide novel ideas for diagnosis and prognosis of TSCC patients, as well as molecular targets for treatment of TSCC. MicroRNAs (miRNAs) are small noncoding RNAs that inhibit gene expression through the 3' untranslated regions (3'UTRs) of their target messenger RNAs. They play crucial roles in numerous biological processes, including cancer progression. Although great efforts have been made, what role miRNAs may play in the early detection and diagnosis of TSCC is not fully understood. Recently, our team has performed a series of basic and clinical researches in an attempt to investigate the relationships between miRNA expressions and prognosis of patients with TSCC and the mechanisms under regulation of TSCC. The results showed that miR-195, miR-34a, miR-29b, miR-375 and miR-26a could inhibit TSCC cells progression and development via a sophisticated network of genes. Specifically, the anti-tumor effects of miR-195 in TSCC may be partially mediated by its inhibition of CyclinD1 and Bcl-2 expression. The expression of miR-34a could inhibit migration and invasion of TSCC cell lines via targeting MMP9 and MMP14. The function of miR-29b may be through the miR-29b/Sp1/PTEN/AKT axis. Overexpression of miR-375 inhibited Sp1 expression by targeting the 3' untranslated region of the Sp1 transcript. MEG3 and miR-26a inhibited TSCC cell proliferation, cycle progression and promoted cell apoptosis and miR-26a could increase the MEG3 expression through reduction of the expression of DNMT3B in TSCC. In light of the role of those miRNAs in diagnosis and prognosis of TSCC, we reported that decreased miR-195 and miR-375 expression was associated with poor overall survival rate of the TSCC patients, while miR-34a expression was negatively correlated with cervical lymph node metastases. Furthermore, combined low expression levels of miR-26a and MEG3 emerged as an independent prognostic factor for poor clinical outcomes in TSCC patients, suggesting that combined miR-26a and MEG3 expression might prove useful as an independent biomarker of clinical prognosis among TSCC patients.

Expression, regulation and roles of miR-26a and MEG3 in tongue squamous cell carcinoma.

MicroRNA miR-26a and long noncoding RNA (lncRNA) MEG3 gene have been independently reported to be tumor suppressor genes in various cancers, but neither has been previously associated with tongue squamous cell carcinoma (TSCC). We report here that miR-26a and lncRNA MEG3 gene expression were both strongly reduced in TSCC compared with levels in matched nonmalignant tissues, and combined low expression levels of both miR-26a and MEG3 emerged as an independent prognostic factor for poor clinical outcome in TSCC patients. Assays in the human TSCC cell lines SCC-15 and CAL27 showed that miR-26a targets the DNA methyltransferase 3B transcript and that its inhibition may result in the upregulation of MEG3, providing a plausible link between the observed reduction of miR-26a and MEG3 in TSCC tissue. Furthermore, the overexpression of miR-26a or MEG3 in SCC-15 and CAL27 cells inhibited cell proliferation and cell cycle progression, and promoted cell apoptosis. Considering the poor prognostic outcomes associated with reduced miR-26a and MEG3, our findings imply that these factors likely play important antitumor effects in TSCC pathogenesis. Furthermore, they represent potential prognostic biomarkers for stratification of TSCC patients.

[Radioactivity seeds interstitial brachytherapy treating malignant salivary gland tumors].

OBJECTIVE: To detect the efficacy of (125)I radioactive seeds implanting treating malignant salivary gland tumors. METHODS: Forty-three patients with malignant salivary gland tumors of head neck were treated with (125)I radioactivity seeds interstitial brachytherapy at Peking University Stomatologic Hospital between 2001 and 2008. These patients were implanted with (125)I radioactivity seeds with the dosage of 120 to 160 Gy. The treatment response, local control rate and survival rate were evaluated and the adverse events observed. RESULTS: Twenty-nine patients had complete remission (CR)of their tumors, and seven patients partial remission (PR), The response rate was 83.7%. The patients were followed up for 8 to 48 months (median 21 months). The local control rate was 79%, and total survival rate 76.7%. No serious side radiotherapeutic effect was observed. CONCLUSION: Radioactivity seeds interstitial brachytherapy is an effective form of treatment for patients with unresectable malignant salivary gland tumors.

Clinicopathological characteristics and outcomes of squamous cell carcinoma of the tongue in different age groups.

BACKGROUND: The clinicopathological features and outcomes of squamous cell carcinoma (SCC) of the tongue in patients of different age groups remain debatable. METHODS: Medical records of 457 patients with tongue SCC were reviewed, grouped by age, followed up, and compared. RESULTS: Sex and TNM stage showed no intergroup differences. Tongue SCC in patients ≤30 years had the most advanced TNM classification and greatest proportion of poorly differentiation tumors. Both disease-free survival (DFS) and disease-specific survival (DSS) showed no statistically significant difference between the youngest and the oldest groups (P = .605 and P = .520). However, there was a tendency of higher death rate caused by recurrence or metastasis in the youngest group compared with the others (91.7% vs 75.4% and 77.4%). CONCLUSION: Young patients had a tendency of higher death rate caused by recurrence or metastasis than middle-age and older patients; therefore, a larger case sample is needed for further confirmation.

miR-34a inhibits migration and invasion of tongue squamous cell carcinoma via targeting MMP9 and MMP14.

BACKGROUND: miR-34a is an important tumor suppressor gene in various cancer types. But little is known about the dysregulation of miR-34a in tongue squamous cell carcinoma (TSCC). In this study, we investigate the expression and potential role of miR-34a in TSCC. METHODS: We evaluated miR-34a expression and its relationship with clinicopathological characters in 75 pairs of TSCC samples, and confirmed the role of miR-34a for predicting lymph node metastases from a further 15 pairs of paraffin-embedded TSCC specimens with stringent clinicopathological recruitment criteria using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effects of miR-34a on cell proliferation, migration and invasion were examined in TSCC cell lines using Cell Counting Kit-8 assay, wound healing assay and transwell assay, respectively. The effects of miR-34a on the expression of matrix metalloproteinase (MMP) 9 and 14 were detected by luciferase reporter assays and Western blot analysis. The expression of miR-34a, MMP9 and MMP14 were also confirmed in TSCC samples by in situ hybridization and immunohistochemistry. RESULTS: miR-34a expression in tumor tissues from TSCC patients with positive lymph node metastases was significantly lower than that with negative lymph node metastases. Overexpression of miR-34a significantly suppressed migration and invasion in TSCC cells and simultaneously inhibited the expression of MMP9 and MMP14 through targeting the coding region and the 3'untranslated region, respectively. Moreover, miR-34a expression in TSCC was inversely correlated with protein expression of MMP9 and MMP14 in the TSCC samples. CONCLUSIONS: miR-34a plays an important role in lymph node metastases of TSCC through targeting MMP9 and MMP14 and may have potential applications in prognosis prediction and gene therapy for lymph node metastases of TSCC patients.

miR-29b suppresses proliferation, migration, and invasion of tongue squamous cell carcinoma through PTEN-AKT signaling pathway by targeting Sp1.

OBJECTIVES: miR-29b has been implicated in various cancers. However, the role of miR-29b in tongue squamous cell carcinoma (TSCC) remains unclear. This study aimed to investigate the role of miR-29b in TSCC progression. MATERIALS AND METHODS: The expression of miR-29b was analyzed in TSCC tissues and cells. Functional studies were performed in TSCC cells. Real time-PCR, Western blot, cell proliferation, transwell, and dual luciferase reporter assays were performed according to standard procedures. RESULTS: miR-29b was significantly decreased in TSCC specimens and cell lines compared with corresponding normal counterparts. Overexpression of miR-29b significantly inhibited the proliferation, migration, invasion, and cell-cycle progression of TSCC cells, and promoted apoptosis. Moreover, miR-29b targeted the 3' untranslated region of the Sp1 transcript and resulted in the deregulation of Sp1. The inhibition of Sp1 by miR-29b subsequently resulted in the upregulation of PTEN, leading to a decline of phosphorylated AKT. Knockdown of Sp1 in TSCC cell lines mimicked the effects of miR-29b overexpression. In addition, the expression of miR-29b was inversely correlated with Sp1 and positively correlated with the PTEN in TSCC specimens. CONCLUSION: miR-29b functions as a tumor suppressor in TSCC, and the miR-29b/Sp1/PTEN/AKT axis might represent a potential therapeutic target for TSCC intervention.

Prognostic implications of micoRNA miR-195 expression in human tongue squamous cell carcinoma.

BACKGROUND: miR-195 is aberrantly expressed in multiple types of disease. But little is known about the dysregulation of miR-195 in tongue squamous cell carcinoma (TSCC). In this study, we investigated the roles of miR-195 in the development and progression of TSCC. METHODS: Using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we evaluated miR-195 expression in TSCC samples from 81 patients. Overall survival of these patients was examined using Kaplan-Meier curves with log-rank tests and the Cox proportional hazards model. The expression of two known miR-195 target genes, Cyclin D1 and Bcl-2, was also examined in the TSCC samples by immunohistochemistry. The effects of miR-195 overexpression on cell cycle progression and apoptosis and its effects on the expression of Cyclin D1 and Bcl-2 were examined in transfected TSCC cell lines (SCC-15 and Cal27) using fluorescence-activated cell sorting assays, luciferase reporter assays, and Western blots. RESULTS: Reduced miR-195 expression was associated with tumor size and the clinical stage of TSCC tumors. Kaplan-Meier survival analysis indicated that the TSCC patients with reduced expression of miR-195 had poor overall survival and in multivariable analyses low levels of miR-195 emerged as an independent prognostic factor for this clinical outcome. Levels of miR-195 expression were inversely correlated with the expression of Cyclin D1 and Bcl-2. Overexpression of miR-195 inhibited cell cycle progression, promoted apoptosis, and reduced Cyclin D1 and Bcl-2 expression in two TSCC cell lines. CONCLUSIONS: miR-195 may have potential applications as a prognostic factor for TSCC patients.

Osteoblastoma of the maxilla and mandible: a report of 2 cases and literature review.

Osteoblastoma is a very rare primary bone tumour in the maxillofacial region. We report 2 cases of osteoblastoma in the maxilla and mandible, respectively. Histologically, the tumour is composed of small, irregular bony trabeculae and osteoids that are separated by a vascular stroma, and it should be considered in the differential diagnosis of an osteoblastic lesion. Total surgical resection is recommended. The absence of recurrence is largely due to adequate initial treatment.