Extracellular vesicle-circEHD2 promotes the progression of renal cell carcinoma by activating cancer-associated fibroblasts.

BACKGROUND: The encapsulation of circular RNAs (circRNAs) into extracellular vesicles (EVs) enables their involvement in intercellular communication and exerts an influence on the malignant advancement of various tumors. However, the regulatory role of EVs-circRNA in renal cell carcinoma (RCC) remains elusive. METHODS: The in vitro and in vivo functional experiments were implemented to measure the effects of circEHD2 on the phenotype of RCC. The functional role of EVs-circEHD2 on the activation of fibroblasts was assessed by collagen contraction assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). The mechanism was investigated by RNA pull-down assay, RNA immunoprecipitation, chromatin isolation by RNA purification, luciferase assay, and co-immunoprecipitation assay. RESULTS: We demonstrated that circEHD2 was upregulated in RCC tissues and serum EVs of RCC patients with metastasis. Silencing circEHD2 inhibited tumor growth in vitro and in vivo. Mechanistic studies indicated that FUS RNA -binding protein (FUS) accelerated the cyclization of circEHD2, then circEHD2 interacts with tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH), which acts as a bridge to recruit circEHD2 and Yes1-associated transcriptional regulator (YAP) to the promoter of SRY-box transcription factor 9 (SOX9); this results in the sustained activation of SOX9. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) regulates the package of circEHD2 into EVs, then EVs-circEHD2 transmits to fibroblasts, converting fibroblasts to cancer-associated fibroblasts (CAFs). Activated CAFs promote the metastasis of RCC by secreting pro-inflammatory cytokines such as IL-6. Furthermore, antisense oligonucleotides (ASOs) targeting circEHD2 exhibited a strong inhibition of tumor growth in vivo. CONCLUSIONS: The circEHD2/YWHAH/YAP/SOX9 signaling pathway accelerates the growth of RCC. EVs-circEHD2 facilitates the metastasis of RCC by converting fibroblasts to CAFs. Our results suggest that EVs-circEHD2 may be a useful biomarker and therapeutic target for RCC.

Circular RNA hsa_circ_0061395 accelerates hepatocellular carcinoma progression via regulation of the miR-877-5p/PIK3R3 axis.

BACKGROUND: Circular RNA hsa_circ_0061395 (circ_0061395) has been reported to accelerate the advancement of hepatocellular carcinoma (HCC). However, the regulatory mechanism by which circ_0061395 modulates the progression of HCC is unclear. METHODS: The morphology and size of exosomes were analyzed by transmission electron microscope (TEM) and nanoparticle-tracking analysis (NTA). Protein levels were detected by western blotting. Expression levels of circ_0061395, microRNA (miR)-877-5p, and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) mRNA were assessed by quantitative real time polymerase chain reaction (qRT-PCR). The proliferation, invasion, migration, cell cycle progression, and apoptosis were analyzed by cell counting kit-8 (CCK-8), plate clone, transwell, or flow cytometry assays. The targeting relationship between circ_0061395 or PIK3R3 and miR-877-5p was verified using the dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. Xenograft assay was performed to confirm the biological function of circ_0061395 in HCC. RESULTS: Circ_0061395 was upregulated in HCC tissues, serum, cells, and serum-derived exosomes. Circ_0061395 silencing decreased tumor growth in vivo, and induced cell cycle arrest, apoptosis, repressed proliferation, invasion, and migration of HCC cells in vitro. MiR-877-5p was downregulated while PIK3R3 was upregulated in HCC. Circ_0061395 regulated PIK3R3 expression via competitively binding to miR-877-5p. MiR-877-5p inhibitor overturned circ_0061395 knockdown-mediated influence on malignant behaviors of HCC cells. PIK3R3 overexpression reversed the suppressive influence of miR-877-5p mimic on malignant behaviors of HCC cells. CONCLUSION: Circ_0061395 facilitated HCC progression via regulating the miR-877-5p/PIK3R3 axis, providing a new perspective on the advancement of HCC.

Bundle geodesic convolutional neural network for diffusion-weighted imaging segmentation.

Purpose: Applying machine learning techniques to magnetic resonance diffusion-weighted imaging (DWI) data is challenging due to the size of individual data samples and the lack of labeled data. It is possible, though, to learn general patterns from a very limited amount of training data if we take advantage of the geometry of the DWI data. Therefore, we present a tissue classifier based on a Riemannian deep learning framework for single-shell DWI data. Approach: The framework consists of three layers: a lifting layer that locally represents and convolves data on tangent spaces to produce a family of functions defined on the rotation groups of the tangent spaces, i.e., a (not necessarily continuous) function on a bundle of rotational functions on the manifold; a group convolution layer that convolves this function with rotation kernels to produce a family of local functions over each of the rotation groups; a projection layer using maximization to collapse this local data to form manifold based functions. Results: Experiments show that our method achieves the performance of the same level as state-of-the-art while using way fewer parameters in the model ( < 10 % ). Meanwhile, we conducted a model sensitivity analysis for our method. We ran experiments using a proportion (69.2%, 53.3%, and 29.4%) of the original training set and analyzed how much data the model needs for the task. Results show that this does reduce the overall classification accuracy mildly, but it also boosts the accuracy for minority classes. Conclusions: This work extended convolutional neural networks to Riemannian manifolds, and it shows the potential in understanding structural patterns in the brain, as well as in aiding manual data annotation.

N-Substitution of acridone with electron-donating groups: crystal packing, intramolecular charge transfer and tuneable aggregation induced emission.

Acridone derivatives with electron-rich triphenylamine functionalized at the amino position were synthesized and their properties were experimentally and computationally investigated. The single crystal structure analysis revealed that the π-π interaction of acridone and the formation of hydrogen bonds of carbonyl and the hydrogen atoms of the pending phenyl ring were crucial in the determination of molecular packing in the crystalline state. An intramolecular charge transfer (ICT) process was observed between acridone and triphenylamine even with reduced conjugation by the nitrogen atom of acridone. Tuneable aggregation induced emissions with blue and green fluorescence were found due to the different aggregation state and particle size, which varied according to the water content in THF. Furthermore, the size of the spacer between acridone and the appended amine was also important in adjusting the property of aggregation induced emission or aggregation caused quenching in the solid state.