Recently, long non-coding RNAs (lncRNAs) have emerged as new gene regulators and prognostic markers in several types of cancer, including renal cell carcinoma (RCC). In this study, we identified an upregulated lncRNA, DLX6-AS1, in RCC tumor tissues compared with normal kidney tissues. Our data suggested that DLX6-AS1 promoted RCC cell growth and tumorigenesis via targeting miR-26a. In addition, we observed that PTEN overexpression restored the renal cancer cell growth and also rescued the RCC tumorigenesis. In summary, we conclude that DLX6-AS1 promotes renal cell carcinoma development via regulation of miR-26a/PTEN axis.
The essence of tissue engineering is the fabrication of autologous cells or induced stem cells in naturally derived or synthetic scaffolds to form specific tissues. Polymer is thought as an appealing source of cell-seeded scaffold owing to the diversity of its physicochemical property and can be electrospun into nano-size to mimic natural structure. Poly (L-lactic acid) (PLLA) and poly (ε-caprolactone) (PCL) are both excellent aliphatic polyester with almost “opposite” characteristics. The controlling combination of PLLA and PCL provides varying properties and makes diverse applications. Compared with the copolymers of the same components, PLLA/PCL blend demonstrates its potential in regenerative medicine as a simple, efficient and scalable alternative. In this study, we electrospun PLLA/PCL blends of different weight ratios into nanofibrous scaffolds (NFS) and their properties were detected including morphology, porosity, degradation, ATR-FTIR analysis, stress-stain assay, and inflammatory reaction. To explore the biocompatibility of the NFS we synthesized, human adipose-derived stem cells (hASCs) were used to evaluate proliferation, attachment, viability and multi-lineage differentiation. In conclusion, the electrospun PLLA/PCL blend nanofibrous scaffold with the indicated weight ratios all supported hASCs well. However, the NFS of 1/1 weight ratio showed better properties and cellular responses in all assessments, implying it a biocompatible scaffold for tissue engineering.
Development and selection of an ideal scaffold is of importance for tissue
engineering. Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) is a
biocompatible bioresorbable copolymer that belongs to the polyhydroxyalkanoate
family. Because of its good biocompatibility, PHBHHx has been widely used as a cell
scaffold for tissue engineering. This review focuses on the utilization of
PHBHHx-based scaffolds in tissue engineering. Advances in the preparation,
modification, and application of PHBHHx scaffolds are discussed.
BackgroundCalcium oxalate monohydrate (COM) is the major crystalline component in kidney stones and its adhesion to renal tubular cells leads to tubular injury. However, COM-induced toxic effects in renal tubular cells remain ambiguous. MicroRNAs (miRNAs) play an important role in gene regulation at the posttranscriptional levels.ObjectiveThe present study aimed to assess the potential changes in microRNAs of proximal renal tubular cells in response to the adhesion of calcium oxalate monohydrate (COM) crystals.MethodologyLactate dehydrogenase (LDH) activity and DAPI staining were used to measure the toxic effects of HK-2 cells exposed to COM crystals. MicroRNA microarray and mRNA microarray were applied to evaluate the expression of HK-2 cells exposed to COM crystals. Quantitative real-time PCR (qRT-PCR) technology was used to validate the microarray results. Target prediction, Gene Ontology (GO) analysis and pathway analysis were applied to predict the potential roles of microRNAs in biological processes.Principal FindingsOur study showed that COM crystals significantly altered the global expression profile of miRNAs in vitro. After 24 h treatment with a dose (1 mmol/L), 25 miRNAs were differentially expressed with a more than 1.5-fold change, of these miRNAs, 16 were up-regulated and 9 were down-regulated. A majority of these differentially expressed miRNAs were associated with cell death, mitochondrion and metabolic process. Target prediction and GO analysis suggested that these differentially expressed miRNAs potentially targeted many genes which were related to apoptosis, regulation of metabolic process, intracellular signaling cascade, insulin signaling pathway and type 2 diabetes.ConclusionOur study provides new insights into the role of miRNAs in the pathogenesis associated with nephrolithiasis.
The use of SonoVue combined with ultrasound exposure increases the transfection efficiency of short interfering RNA (siRNA). The objective of this study was to prepare targeted nanobubbles (TNB) conjugated with NET-1 siRNA and an antibody GPC3 to direct nanobubbles to hepatocellular carcinoma cells. SMMC-7721 human hepatocellular carcinoma cells were treated with six different groups. The transfection efficiency and cellular apoptosis were measured by flow cytometry. The protein and messenger RNA (mRNA) expression were measured by Western blot and quantitative real-time PCR, respectively. The migration and invasion potential of the cells were determined by Transwell analysis. The results show that US-guided siRNA-TNB transfection effectively enhanced gene silencing. In summary, siRNA-TNB may be an effective delivery vector to mediate highly effective RNA interference in tumor treatment.
The aim of this study was to establish a novel targeting nanobubble (TNB) conjugated with small interfering RNA (siRNA)‐cyanine 5 (Cy5) and to validate its theranostic ability in vivo. The TNB conjugated with neuroepithelial transforming gene 1 (NET‐1) siRNA‐Cy5 was prepared by thin‐film hydration and mechanical sonication method. A hepatocellular carcinoma (HCC) xenograft model was established by subcutaneously injecting SMMC‐7721 cells in BALB/c nude mice. The NET‐1 siRNA‐conjugated TNB was utilized for accurate contrast‐enhanced ultrasound in vivo imaging, which was enabled by the target ligand GPC‐3 antibody and specific gene transfection with the aid of low‐frequency ultrasound (LFUS) irradiation. BALB/c nude mice bearing tumors were randomized into 5 groups and irradiated with LFUS for 5 min after TNB administration; mice were treated twiceaweek for atotal of 60 d. The mean particle size of TNB was <500 nm. Mice treated with NET‐1 siRNA‐conjugated TNB showed a significant decrease in tumor growth and the highest survival rate. Our findings offer an effective and safe gene vehicle and probe for molecular imaging in vivo. It may improve the early diagnosis and treatment effects of HCC.—Wu, B., Shang, H., Liang, X., Sun, Y., Jing, H., Han, X., Cheng, W. Preparation of novel targeting nanobubbles conjugated with small interfering RNA for concurrent molecular imaging and gene therapy in vivo. FASEB J. 33, 14129‐14136 (2019). http://www.fasebj.org
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