BackgroundThe deregulation of microRNAs has been reported to play a pivotal role in hepatocellular carcinoma (HCC). MiR-126-3p has been reported to be associated with poor prognosis in HCC. However the underlying mechanism of miR-126-3p in HCC remains unclear.MethodsThe expression levels of miR-126-3p in HCC tissues and cells were detected by RT-PCR. Transwell assay and capillary tube formation assay were applied to assess the metastasis and angiogenesis in vitro. Nude mice subcutaneous tumor model was used to perform in vivo study. Dual- luciferase reporter assay was conducted to confirm the direct binding of miR-126-3p and target genes. The changes of biomarker protein levels were examined by western blot and Immunohistochemistry.ResultsWe observed that the miR-126-3p expression levels in HCC tissues and cells were significantly down-regulated. Through gain- and loss- of function studies, we showed that miR-126-3p dramatically inhibited HCC cells from migrating and invading extracellular matrix gel and suppressed capillary tube formation of endothelial cells in vitro. Furthermore, overexpression of miR-126-3p significantly reduced the volume of tumor and microvessel density in vivo. LRP6 and PIK3R2 were identified as targets of miR-126-3p. Silencing LRP6 and PIK3R2 had similar effects of miR-126-3p restoration on metastasis and angiogenesis individually in HCC cells. Furthermore, the miR-126-3p level was inversely correlated with LRP6 and PIK3R2 in HCC tissues. In addition, the rescue experiments indicated that the metastasis and angiogenesis functions of miR-126-3p were mediated by LRP6 and PIK3R2.ConclusionOur results demonstrates that deregulation of miR-126-3p contributes to metastasis and angiogenesis in HCC. The restoration of miR-126-3p expression may be a promising strategy for HCC therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0259-1) contains supplementary material, which is available to authorized users.

Pancreatic cancer is one of the most aggressive cancers worldwide with a high mortality rate. Prognosis remains poor even in this era of advanced medicine mainly due to early metastasis and invasion. The present study aimed to explore and validate predictors of distant metastasis and prognosis in pancreatic cancer. In our preliminary experiment, we established a novel metastatic pancreatic cancer cell line BxPC-M8 from parent BxPC-3 cells. Via whole genome sequencing, RT-qPCR, western blotting, migration and invasion assays, we initially found that BxPC-M8 shared similar biological characteristics to BxPC-3, but only differed in enhanced metastatic and invasive capabilities with a significant increase in collagen type VI α1 chain (COL6A1) expression. Knockdown of COL6A1 via small interfering RNA led to a significant decrease in migration and invasion of BxPC-M8 cells, suggesting suppressed epithelial-mesenchymal transition. Furthermore, a significant increase in COL6A1 expression was observed in cancerous tissue compared with paracancerous tissue (40.7 vs 3.7, P=0.001). Additionally, its expression was observed to be significantly associated with distant metastasis and vascular invasion at the time of surgery. Multivariate analysis revealed that COL6A1 expression (hazard ratio 1.90, 95% confidence interval 1.04-3.47, P=0.037) is an independent predictor of overall survival (OS). The median OS observed for COL6A1 + and COL6A1patients was found to be 8±4 and 14±7 months (P= 0.021), respectively. Of note, we identified that COL6A1 expression in tissue samples was associated with significantly reduced OS (P= 0.001), demonstrating that COL6A1 may serve an important role in the metastatic process and could be considered as a predictor of poor outcomes in patients with pancreatic cancer. In addition, our findings suggest that COL6A1 could be an indicator of distant metastasis and a valid prognostic predictor in such patients; however, further investigation is required.

In spinal degenerative disease, an injectable liquid hydrogel can fill in defect entirely, lessen the danger of implant relocation and following loss of disc height, minimizing the operative trauma. Here, we propose an injectable in-situ chemically cross-linked hydrogel by a two-component reaction of liquid silk fibroin with liquid polyurethane at physiological temperature conditions. Confined compression tests and fatigue tests were reported to assess physical properties of the hydrogel. Impact of different diameter on the biomechanical behaviours was tested to evaluate the clinical potentiality of the hydrogel for replacing nucleus pulposus. Degradation behaviours in different solutions and animal experiments were also investigated to examine the tissue biocompatibility of the hydrogel. The hydrogel modulus was affected by the hydrogel geometrical (diameter) parameters. SF/PU composite hydrogel can survive a million cycles, unconstrained fatigue resistance. More importantly, in vivo biocompatibility using New Zealand white rabbits, showed good biocompatibility over a three-month period in culture. Particularly, they showed the significant clinical merit of providing stronger axial compressive stiffness on confined compression test. Based on the outcomes of the present research, the SF/PU composite hydrogel may provide significant advantages for use in future clinical application in replacing nucleus pulposus field.

To date, only 20 cases of Epstein–Barr virus (EBV)-associated intrahepatic cholangiocarcinomas (IHCCs) have been reported in the literature.Pathology records of IHCC from January 1, 2007 to December 31, 2013 were retrieved from our hospital. Clinical information related to EBV-associated IHCC were also obtained, including gender, age at initial diagnosis, tumor size, tumor–node–metastasis stage, and follow-up duration. Surgically resected stage-matched EBV-negative IHCCs with full follow-up were selected for comparison. All liver specimens were fixed in 10% neutral-buffered formalin and paraffin-embedded tissue blocks containing cholangiocarcinoma and nonneoplastic liver tissue. Hematoxylin and eosin-stained sections were present in all cases.Among 329 primary IHCC patients, intranuclear expression of EBV was only found in 11 patients (3.3%), with an age range of 30 to 67 years (mean, 53.2 years; median, 54 years). The group consisted of 4 male and 7 female patients (M:F ratio 1:1.8). Histopathological analysis showed 1 case (9.1%) belonged to the typical lymphoepithelioma-like carcinoma (LELC), primarily composed of undifferentiated tumor cells intimately admixed with abundant lymphoplasmacytic cells. Two cases (18.2%) belonged to the conventional-type IHCCs, showing irregularly shaped neoplastic glands and scattered lymphoplasmacytic infiltration. The remaining 8 cases (72.7%) belonged to the lymphoepithelioma-like cholangiocarcinomas (LELCCs), showing varied glandular differentiation and dense lymphoplasmacytic infiltration. The overall survival of EBV-positive IHCCs was not significantly different from that of EBV-negative IHCCs (P = 0.512).Our data demonstrate that EBV-associated IHCC is very rare and may be subclassified into 3 different pathological types including LELC, conventional-type IHCC and LELCC on the basis of the tumor cellular differentiation, and host cellular immune responses in the tumors. The etiological, clinical, pathological, and molecular features are needed to be future studied by multicentric efforts in recruiting more EBV-associated IHCC patients.