Snail-mediated epithelial-mesenchymal transition (EMT) process plays a fundamental role in facilitating pancreatic ductal adenocarcinoma (PDAC) stemness and metastasis. In the present study, we revealed that microRNA-30 (miR-30) members, especially miR-30b, were remarkably downregulated in triple-positive (CD24+, CD44+, EpCAM+) pancreatic cancer stem cells (PCSCs). In addition, we revealed that miR-30b suppressed EMT process in PCSCs. Overexpression of miR-30b led to reduced expression of mesenchymal marker N-cadherin and the upregulation of epithelial marker E-cadherin. Moreover, both of TargetScan and PicTar algorithms predicted that miR-30b directly targeted Snail 3'UTR. Luciferase reporter assay showed that miR-30b could specifically reduce the translational activity of Snail wild-type 3'UTR, but not its mutant form. In line with these results, transwell assay demonstrated that overexpression of miR-30b mimic impaired migratory and invasive capacities of PCSCs. Furthermore, miR-30b overexpression suppresses in vivo tumorigenic potential of PDACs. Finally, a negative correlation between the expression of miR-30b and Snail was uncovered. Low level of miR-30b and high Snail expression both predict dismal prognosis in PDAC patients. Taken together, these findings implicate that miR-30b may suppress PCSC phenotype and PDAC metastasis through posttranscriptionally suppressing Snail expression, highlighting that miR-30b may serve as a therapeutic agent in the treatment of PDAC.

Background The regulatory mechanism of insulin-producing cells (IPCs) differentiation from induced pluripotent stem cells (iPSCs) in vitro is very important in the phylogenetics of pancreatic islets, the molecular pathogenesis of diabetes, and the acquisition of high-quality pancreatic β-cells derived from stem cells for cell therapy. Methods miPSCs were induced for IPCs differentiation. miRNA microarray assays were performed by using total RNA from our iPCs-derived IPCs containing undifferentiated iPSCs and iPSCs-derived IPCSs at day 4, day 14, and day 21 during step 3 to screen the differentially expressed miRNAs (DEmiRNAs) related to IPCs differentiation, and putative target genes of DEmiRNAs were predicted by bioinformatics analysis. miR-690 was selected for further research, and MPCs were transfected by miR-690-agomir to confirm whether it was involved in the regulation of IPCs differentiation in iPSCs. Quantitative Real-Time PCR (qRT-PCR), Western blotting, and immunostaining assays were performed to examine the pancreatic function of IPCs at mRNA and protein level respectively. Flow cytometry and ELISA were performed to detect differentiation efficiency and insulin content and secretion from iPSCs-derived IPCs in response to stimulation at different concentration of glucose. The targeting of the 3′-untranslated region of Sox9 by miR-690 was examined by luciferase assay. Results We found that miR-690 was expressed dynamically during IPCs differentiation according to the miRNA array results and that overexpression of miR-690 significantly impaired the maturation and insulinogenesis of IPCs derived from iPSCs both in vitro and in vivo. Bioinformatic prediction and mechanistic analysis revealed that miR-690 plays a pivotal role during the differentiation of IPCs by directly targeting the transcription factor sex-determining region Y (SRY)-box9. Furthermore, downstream experiments indicated that miR-690 is likely to act as an inactivated regulator of the Wnt signaling pathway in this process. Conclusions We discovered a previously unknown interaction between miR-690 and sox9 but also revealed a new regulatory signaling pathway of the miR-690/Sox9 axis during iPSCs-induced IPCs differentiation. Electronic supplementary material The online version of this article (10.1186/s13287-019-1154-8) contains supplementary material, which is available to authorized users.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Ubiquitin-proteasome system has been shown to play a pivotal role in the pathophysiology of HCC and other malignancies. UBE2Q1 is a putative E2 ubiquitin conjugating enzyme, and may be involved in the regulation of cancer-related proteins. In this study, we investigated the expression pattern of UBE2Q1 in HCC cell lines and human HCC specimens, and its potential clinical and biological significance in HCC. Western blot and immunohistochemical analyses revealed that UBE2Q1 was significantly upregulated in HCC tumorous tissues compared with the adjacent noncancerous ones. Next, univariate and multivariate survival analyses were performed to determine the prognostic significance of UBE2Q1 in HCC. The results showed that upregulated expression of UBE2Q1 was positively correlated with high histological grades of HCC and predicted poor prognosis. In addition, the expression of UBE2Q1 was progressively increased in serum-refed HCC cells. UBE2Q1 depletion by small interfering RNA inhibited cell proliferation and led to G1 phase arrest in HepG2 and BEL-7404 cells. Furthermore, we showed that cells transfected with UBE2Q1-targeting siRNA resulted in significant increase in the levels of p53, p21 in HepG2 and BEL-7404 cells. These data imply that UBE2Q1 is upregulated in liver cancer cell lines and tumorous samples and may play a role in the development of HCC.

ErbB3 binding protein 1 (EBP1) has been recently reported to function as a tumor suppressor in the progression of multiple cancers, including breast cancer, prostate cancer, salivary adenoid cystic carcinoma (ACC), and oral squamous cell carcinoma (OSCC). However, the expression and physiological significance of EBP1 in hepatocellular carcinoma (HCC) remain unclear. In the study, we showed that EBP1 was significantly downregulated in clinical HCC specimens, and that decreased expression of EBP1 was associated with enhanced proliferation in HCC cells. Western blot and immunohistochemical analyses revealed that EBP1 was remarkably downregulated in HCC tissues compared with the adjacent normal ones. The levels of EBP1 were significantly associated with histological grade (P = 0.034), tumor size (P = 0.001), and Ki67 expression (P < 0.001) in HCC specimens. Univariate and multivariate analyses showed that EBP1 could serve as an independent prognostic indicator of patients' survival. Serum starvation and refeeding assay indicated that EBP1 was accumulated in growth-arrested HCC cells, and was progressively decreased when cells entered into S phase. Moreover, the depletion of EBP1 induced growth acceleration and cell cycle progression in L02 hepatocytes. On the basis of these findings, we conclude that EBP1 may be a valuable prognostic marker and promising therapeutic target of HCC.

Pancreas transplantation is considered as a promising therapeutic option with the potential to cure diabetes. However, efficacy of current clinical transplantation is limited by the donor organ. With regard to creating a functional pancreas-tissue equivalent for transplantation, vascularization remains a large obstacle. To enhance the angiogenic properties of pancreatic decellularized scaffold, surface modification of the vasculature was used to promote endothelialization efficiency. In this study, an endothelialized pancreatic decellularized scaffold was obtained through heparin modification under mild conditions. The immobilization of heparin was performed through 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide and N-Hydroxysuccinimide. The morphology, ultra-structure and porosity of the heparinized scaffold were characterized by toluidine blue staining, scanning electron microscope and infrared spectrum. The adhesion, proliferation and angiogenesis of human umbilical vein endothelial cells on heparin-pancreatic decellularized scaffold were also researched in vitro. In vivo transplantation was also performed to observe the location of human umbilical vein endothelial cells and the formation of new blood vessel, which exhibited significant differences with pancreatic decellularized scaffold group (p<0.05). These findings indicated that the endothelialized heparin-pancreatic decellularized scaffold may be used to solve the problem of blood supply and to support the function of insulin-secreting cells better after in vivo transplantation, and therefore, would be a potential candidate for pancreatic tissue engineering.