Dysregulation of microRNA expression is involved in several pathological activities associated with gastric cancer progression and chemo-resistance. However, the role and molecular mechanisms of miR-363 in the progression and chemoresistance of gastric cancer remain enigmatic. In this study, we validated that miR-363 expression was higher in gastric cancer tissues than in adjacent normal tissues. Multivariate analysis identifies high levels of miR-363 expression as an independent predictor for postoperative recurrence and lower overall survival. Increased miR-363 expression promotes gastric cancer cell proliferation and chemo-resistance through directly targeting the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7). Clinically, our data reveal that overexpression of miR-363 correlates with the poor survival outcomes in patients with gastric cancer, and docetaxel + cisplatin + 5-FU (DCF) regimen response is impaired in patients with miR-363 overexpression. These data suggest that miR-363 may be a potential therapeutic target for gastric cancer and serve as a biomarker for predicting response to DCF regimen treatment.
Colorectal cancer (CRC) is one of the most common cancers worldwide, with a particularly high incidence in developed countries. Distant metastasis and recurrence are the main causes of CRC-related deaths. MicroRNAs (miRNAs) in the serum make them potential biomarkers for cancers, as reported in serum or tumor tissues from CRC patients. In this study, we found that miR-612 expression was significantly lower in CRC tissues or cells compared with peritumor tissues or normal cells, and lower in metastatic CRC specimens compared with non-metastatic specimens, whereas AKT2 exhibited opposite trend. Gain-of-function and loss-of-function assays showed that miR-612 inhibited CRC cell proliferation and migration in vitro by Cell Counting Kit-8 and transwell assays. Further analysis revealed that miR-612 directly suppressed AKT2, which in turn inhibited the downstream epithelial–mesenchymal transition-related signaling pathway. These results were additionally validated in vivo by tumorigenesis and liver metastasis experiments. The results of this study suggested a critical role of miR-612 in the development of CRC.
There is a high local recurrence (LR) rate in breast-conserving therapy (BCT) and enhancement of the local treatment is promising as a way to improve this. Thus we propose a drug delivery system using doxorubicin (DOX)-loaded mesoporous silica nanoparticle composite nanofibers which can release anti-tumor drugs in two phases-burst release in the early stage and sustained release at a later stage-to reduce the LR of BCT. In the present study, we designed a novel composite nanofibrous scaffold to realize the efficient release of drugs by loading both DOX and DOX-loaded mesoporous silica nanoparticles into an electrospun PLLA nanofibrous scaffold. In vitro results demonstrated that this kind of nanomaterial can release DOX in two phases, and the results of in vivo experiments showed that this hybrid nanomaterial significantly inhibited the tumor growth in a solid tumor model. Histopathological examination demonstrated that the apoptosis of tumor cells in the treated group over a 10 week period was significant. The anti-cancer effects were also accompanied with decreased expression of Bcl-2 and TNF-α, along with up-regulation of Bax, Fas and the activation of caspase-3 levels. The present study illustrates that the mesoporous silica nanoparticle composite nanofibrous scaffold could have anti-tumor properties and could be further developed as adjuvant therapeutic protocols for the treatment of cancer.
The oxide phases in oxide dispersion strengthened PM2000 steel have been investigated by transmission electron microscopes. Two nano-sized yttrium aluminum oxide phases, YAlO3 having a distorted orthorhombic-simple structure with approximate lattice parameters of a/b/c = 5.4197/5.8520/7.6413 Å and Y3Al5O12 having a tetragonal-simple crystal structure, have been identified in the steel. Two aluminum iron oxide phases and one aluminum titanium oxide phase, which are not known to have been identified previously in steels, have been found in the PM2000 steel. They have been determined to be aluminum iron oxide, Al2Fe2O6 having an orthorhombic crystal structure with the lattice parameters a/b/c = 7.235/5.926/ 7.502 Å, and aluminum iron oxide, Al3FeO6 having a body-centered cubic crystal structure with an average lattice parameter of 3.047 Å, as well as aluminum titanium oxide, Al3Ti5O2 having a face-centered cubic crystal structure with an average lattice parameter of 6.923 Å. The PM2000 steel contains a small amount of Al2Fe2O6, Al3FeO6, Al3Ti5O2 and Al2O3 phases with a large size and block/ or spherical morphology.
Circular RNAs (circRNAs) is a novel class of non-coding RNAs resulting from the non-canonical splicing of linear pre-mRNAs. However, the role of circRNAs in gastric cancer (GC) remains indistinct. This study aims to explore their potential modulation in GC and its prognostic value. We first screen for circRNA expression patterns in GC through GC and adjacent noncancerous tissues by microarray. Based on the bioinformatics analysis of the microarray data, we screened out a novel circRNA, circ-PTPDC1. Then we demonstrated that circ-PTPDC1 was up-regulated in GC cells, tissues, and serum. Its overexpression was positively correlated with age, invasion depth, advanced clinical stages, and worse survival in patients with GC. We further revealed that circ-PTPDC1 promotes the proliferation, migration, and invasion of GC cell lines via sponging miR-139-3p by regulating ELK1. Importantly, we identified that circ-PTPDC1 promotes tumor upgrowth and metabasis in vivo. Additionally, we established its prognostic prediction model based on the follow-up data of the patients. Our study revealed a novel regulatory mechanism and a comprehensive landscape of circ-PTPDC1 in GC, suggesting that circ-PTPDC1 has the potential to be a biomarker for early detection and prognostic prediction of GC.
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