MicroRNA-203 inhibits proliferation and invasion, and promotes apoptosis of osteosarcoma cells by targeting Runt-related transcription factor 2.

Accumulating evidence indicates that microRNA-203 (miR-203) is abnormally expressed in many human tumor tissues and significantly associated with the occurrence, development and clinical outcomes of human tumors. The aim of this study was to determine the target genes and functional significance of miR-203 in osteosarcoma cells. We found reduced expression of miR-203 in osteosarcoma tissues and cells (MG63 and U2-OS) compared with the adjacent normal tissues and normal osteoblastic cells (hFOB1.19), respectively. In vitro studies further demonstrated that exogenous miR-203 overexpression inhibited osteosarcoma cell proliferation and invasion, and promoted apoptosis. At the molecular level, our results confirmed that apoptosis, cell cycle and invasion-related proteins were regulated by miR-203. Our findings also revealed that Runt-related transcription factor 2 (RUNX2) was directly negatively regulated by miR-203. These results suggested that miR-203 may function as a tumor suppressor and may therefore have therapeutic potential in the treatment of human osteosarcoma.

Roles of Cell Cyle Regulators Cyclin D1, CDK4, and p53 in Knee Osteoarthritis.

OBJECTIVE: The aim of this study was to investigate the roles of cyclin D1, CDK4, and p53 in knee osteoarthritis (KOA). METHODS: A total of 76 healthy controls and 154 KOA cases (grades ranging from II to IV) were recruited. Protein expression of cyclin D1, CDK4, and p53 were detected by immunohistochemistry, and mRNA expression levels of the cyclin D1, the CDK4, and the p53 genes were measured by reverse transcription-polymerase chain reaction. RESULTS: Both protein and mRNA expression levels of cyclin D1 and CDK4 were significantly lower in KOA cases than those in healthy controls, while protein and mRNA expression of p53 was significantly higher in KOA cases than that in healthy controls (all p < 0.05). As the grades of KOA increased, Cyclin D1 and CDK4 mRNA expressions decreased, whereas p53 mRNA expression increased (all p < 0.05). In KOA cases, mRNA expression of Cyclin D1 was positively correlated to CDK4 mRNA levels (r = 0.386, p < 0.001), while negatively correlated with p53 mRNA levels (r = -0.227, p = 0.005). CONCLUSIONS: Expression of the Cyclin D1, CDK4, and p53 genes are correlated with the disease grades of KOA.

Association of the XPA A23G polymorphism with the risk of head and neck carcinomas: Evidence from 5,491 subjects.

The XPA gene participates in modulating DNA damage recognition during the DNA nucleotide excision repair process. Current data regarding the association of the XPA A23G polymorphism with the risk of head and neck squamous cell carcinoma (HNSCC) remain controversial, and meta-analyses focusing on the HNSCC risk and this polymorphism are limited. Therefore, the aim of the present study was to derive a more precise estimation of this association by a meta-analysis of all the eligible studies. Odds ratios (ORs) with 95% confidence intervals (CI) were assessed for the strength of the associations in eight studies, including 5,491 subjects (2,409 HNSCC cases and 3,082 controls). The overall analysis revealed that the XPA A23G polymorphism was not significantly associated with the overall HNSCC risk. Consistently, there was no evidence for the association between the XPA A23G polymorphism and HNSCC risk in subgroup analyses based on ethnicity and the source of controls. However, the significant associations in oral carcinoma with the increased risk among the XPA heterozygote (AG vs. AA: OR, 1.58; 95% CI, 1.06-2.37; Pheterogeneity=0.23, I2=30%) and dominant (AG +GG vs. AA: OR, 1.53; 95% CI, 1.04-2.23; Pheterogeneity=0.21, I2=36%) models were observed in the subgroup analysis by tumor site. In conclusion, the meta-analysis suggested that the XPA A23G polymorphism was not associated with overall HNSCC susceptibility, but it was associated with oral carcinoma susceptibility and it may be a risk factor for oral carcinoma. Further well-designed and large studies are required to confirm these associations.

Papillary squamous cell carcinoma of the oral mucosa: a clinicopathologic and immunohistochemical study of 12 cases and literature review.

Papillary squamous cell carcinoma (SCC) (PSCC) of the oral mucosa is a relatively rare but distinct variant of SCC of head and neck. The objectives of this study were to describe the clinicopathologic and immunohistochemical features of a series of patients with oral PSCC and to review the literature on this topic. Retrospective review of patients with clinical and pathologic diagnosis of PSCC (n = 12) between 2000 and 2008 in our institution was conducted. The outcome analysis in a mean follow-up of 56 months (range, 24-131 months) was performed. These patients were 7 women and 5 men, and the mean age at diagnosis was 72.9 years (range, 53-83 years). The cheek and the gingiva were the predominant sites of involvement. At the end of follow-up, 4 patients were found to have local recurrence, and 3 were dead of disease. The estimated 3- and 5-year survival was 91.7% and 76.4% for the whole series, respectively. Histopathologically, the papillary pattern consisted of multiple, thin, delicate filiform, finger-like papillary projections with fibrovascular cores. Besides, the exophytic pattern consisted of the broad-based bulbous to "cauliflower-like" exophytic growth with rounded projections. Immunohistochemically, positivity for CKpan, CKhmw (high molecular weight), and p53, yet negativity for CK8, vimentin, desmin, smooth muscle actin, and S-100 was observed in PSCC. In conclusion, 2 specific histopathologic growth patterns of oral PSCC were identified to separate from conventional SCC. Patients with PSCC have a favorable outcome in relation to exophytic nature and limited invasion of the tumor.

A clinicopathological study on verrucous hyperplasia and verrucous carcinoma of the oral mucosa.

BACKGROUND: Oral verrucous hyperplasia (VH) and verrucous carcinoma (VC) are two clinicopathologically distinctive oral verrucous lesions. The objective of this study was to investigate the clinicopathological features of the two verrucous lesions and estimate their relationship from China. METHODS: Retrospective review of two series of patients with histologically confirmed VH (n = 121) and VC (n = 56) between 1996 and 2009 in our hospital were conducted. RESULTS: The average age of VH was 58.5 years (ratio male:female = 1.37) with the tongue being the predominant site. The average age of VC was 64.3 years (ratio male:female = 1.15) with the lower lip being the predominant site. Multivariate analysis revealed that the elderly patient with verrucous lesion (≥60 years) was associated with 3.06-fold (P = 0.007) increased carcinoma risk compared with the non-elderly patient. The lesion located on lower lip was associated with 13.54-fold (P < 0.001) increased carcinoma risk compared with other sites. CONCLUSION: Clinicopathological features of VH and VC in China were elucidated. Elderly patient with oral verrucous lesion located on the lower lip correlates with higher risk of carcinoma.