HOXD10, a key regulator of cell-differentiated phenotype maintainence, has been demonstrated to be involved in the tumorigenesis of many human malignacies. However, the status of HOXD10 expression and its biological function in cholangiocellular carcinoma (CCC) remain to be clarified. In the present study, we investigated the clinical significance and biological functions of HOXD10 in CCC and found that the expression of HOXD10 and its downstream effector RHOC was significantly different in well-differentiated CCC tissues compared with poorly-differentiated lesions. We also observed a significant correlation between low HOXD10 and high RHOC expression levels and worse prognosis. The stable overexpression of HOXD10 by lentivirus vector significantly inhibited cell invasion partly by downregulating the expression of MMP2 and MMP9, and significantly increased early apoptosis in CCC cell lines and induced G1 phase cell cycle arrest, contributing to the inhibition of cell proliferation in vitro. Additionally, we demonstrated that the inactivation of the RHOC/AKT/MAPK pathway was involved in the tumor-suppressive functions of HOXD10 in CCC. These results suggested that HOXD10 may be a putative suppressor gene and can act as a prognostic marker and potentially a novel therapeutic target for CCC.

Objectives. Temporomandibular joint (TMJ) disorders are common disease in maxillofacial surgery. The aim of this study is to regenerate fibrocartilage with a mixture of TMJ fibrochondrocytes and periodontal ligament derived mesenchymal stem cells (PD-MSCs). Materials and Methods. Fibrochondrocytes and PD-MSC were cocultured (ratio 1 : 1) for 3 weeks. Histology and glycosaminoglycans (GAGs) assay were performed to examine the deposition of GAG. Green florescent protein (GFP) was used to track PD-MSC. Conditioned medium of PD-MSCs was collected to study the soluble factors. Gene expression of fibrochondrocytes cultured in conditioned medium was tested by quantitative PCR (qPCR). Results. Increased proliferation of TMJ-CH was observed in coculture pellets when compared to monoculture. Enhanced GAG production in cocultures was shown by histology and GAG quantification. Tracing of GFP revealed the fact that PD-MSC disappears after coculture with TMJ-CH for 3 weeks. In addition, conditioned medium of PD-MSC was also shown to increase the proliferation and GAG deposition of TMJ-CH. Meanwhile, results of qPCR demonstrated that conditioned medium enhanced the expression levels of matrix-related genes in TMJ-CH. Conclusions. Results from this study support the mechanism of MSC-chondrocyte interaction, in which MSCs act as secretor of soluble factors that stimulate proliferation and extracellular matrix deposition of chondrocytes.

Ras homolog family member C (RHOC) is important during the progression of several types of cancer, including prostate, breast and hepatocellular carcinoma. However, the function of RHOC in cholangiocellular carcinoma (CCC), a highly recurrent and metastatic carcinoma with poor prognosis, remains unclear. The aim of the present study was to investigate the involvement of RHOC in CCC tumor progression. RHOC expression levels were examined in CCC tissues and cells, and adjacent nontumorous bile duct tissues. The effects and molecular mechanisms of RHOC expression on cell migration and invasion were also investigated. The current study demonstrated that RHOC protein was frequently overexpressed in human CCC specimens and CCC cell lines. Downregulation of RHOC inhibited CCC cell invasion and migration partially via inhibition of matrix metalloproteinase 2, 3 and 9 expression. RHOC also modulated the expression of several epithelial-mesenchymal transition (EMT)-associated proteins, including E‑cadherin, vimentin, Slug and Snail, to promote to EMT progression. The present results demonstrated that RHOC is important for the invasion and migration of CCC through simultaneous regulation of MMPs and EMT‑associated protein, suggesting that RHOC is a potential molecular target for CCC treatment.

BackgroundThis retrospective study and meta-analysis was designed to explore the relationship between E-cadherin (E-cad) expression and the molecular subtypes of invasive non-lobular breast cancer, especially in early-stage invasive ductal carcinoma (IDC).MethodsA total of 156 post-operative cases of early-stage IDCs were retrospectively collected for the immunohistochemistry (IHC) detection of E-cad expression. The association of E-cad expression with molecular subtypes of early-stage IDCs was analyzed. A literature search was conducted in March 2016 to retrieve publications on E-cad expression in association with molecular subtypes of invasive non-lobular breast cancer, and a meta-analysis was performed to estimate the relational statistics.ResultsE-cad was expressed in 82.7% (129/156) of early-stage IDCs. E-cad expression was closely associated with the molecular types of early-stage IDCs (P < 0.050); moreover, the molecular subtypes were an independent factor influencing E-cad expression in early-stage IDCs. A total of 12 observational studies (including our study) were included in the meta-analysis. The meta-analytical results show a significantly greater risk of E-cad expression loss in triple-negative breast cancer (TNBC) than in other molecular subtypes (TNBC vs. luminal A: RR = 3.45, 95% CI = 2.79–4.26; TNBC vs. luminal B: RR = 2.41, 95% CI = 1.49–3.90; TNBC vs. HER2-enriched: RR = 1.95, 95% CI = 1.24–3.07).ConclusionsEarly-stage IDCs or invasive non-lobular breast cancers with the TNBC molecular phenotype have a higher risk for the loss of E-cad expression than do tumors with non-TNBC molecular phenotypes, suggesting that E-cad expression phenotypes were closely related to molecular subtypes and further studies are needed to clarify the underlying mechanism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12957-017-1210-8) contains supplementary material, which is available to authorized users.

Introduction Circular RNAs (circRNAs) play critical roles in tumorigenesis, but their clinical efficacy in esophageal squamous cell carcinoma (ESCC) still retains controversial. This meta‐analysis aims at evaluating the associations between circRNA expressions and clinicopathologic features as well as the diagnostic and prognostic values of circRNAs in ESCC. Materials & Methods PubMed, EMBASE, and other online databases were systematically searched to collect studies on circRNAs and clinicopathological features, diagnostic, and/or prognostic assessments of ESCC. The quality of included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS‐2) and Newcastle‐Ottawa Scale (NOS) scales. The included studies were quantitatively weighted and merged, and diagnostic indicators, hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated. P values were merged by Fisher᾽s method. Sources of heterogeneity were traced using subgroup, sensitivity, and meta‐regression analyses. Results As a result, 12 studies were included, representing 769 ESCC patients. The meta‐analysis showed that abnormal expressions of circRNAs were associated to TNM stage as well as lymph node and distant metastases in ESCC cases. CircRNA was used to distinguish ESCC patients from healthy controls, and the merged sensitivity, specificity, and the area under the curve (AUC) of ESCC were 0.78 (95% CI: 0.74–0.81), 0.79 (95% CI: 0.75–0.83), and 0.86, respectively. The survival analysis showed that upregulated oncogenic circRNA levels in ESCC tissues was associated with the shorter overall survival (OS) of the patients (univariate analysis: HR = 2.25, 95% CI: 1.71–2.95, p = 0.000, I2 = 0.0%; multivariate analysis: HR = 2.50, 95% CI: 1.61–3.89, p = 0.000, I2 = 0.0%), while the OS of ESCC patients presenting overexpressions of tumor‐suppressive circRNAs was significantly ameliorated (HR = 0.29, 95% CI: 0.20–0.42, p = 0.000, I2 = 0.0%). The subgroup analyses based on circRNA biofunctions, sample size, and reference gene also revealed robust results. Conclusion CircRNAs can be used as promising molecular biomarkers for the early diagnosis and prognosis monitoring of ESCC.