RNF115 aggravates tumor progression through regulation of CDK10 degradation in thyroid carcinoma.

BACKGROUND: RING Finger Protein 115 (RNF115), a notable E3 ligase, is known to modulate tumorigenesis and metastasis. In our investigation, we endeavor to unravel the putative function and inherent mechanism through which RNF115 influences the evolution of thyroid carcinoma (THCA). METHODS: We analyzed RNF115 expression in THCA using the Cancer Genome Atlas (TCGA) database. The influence of RNF115 on the progression of THCA was evaluated using both in vitro and in vivo experimental approaches. The protein regulated by RNF115 was identified through bioinformatics analysis, and its biological significance was further explored. RESULTS: In both THCA tissues and cells, RNF115 showed elevated expression levels. Enhanced expression of RNF115 fostered cell proliferation, tumor growth, and the exacerbation of epithelial-mesenchymal transition (EMT) in THCA, while also promoting tumor lung metastasis. Bioinformatics analysis identified cyclin-dependent kinase 10 (CDK10) as a downstream target of RNF115, which was found to be ubiquitinated and degraded by RNF115 in THCA cells. Functionally, overexpression of CDK10 was found to counteract the promotion of malignant phenotype in THCA induced by RNF115. From a mechanistic perspective, RNF115 activated the Raf-1 pathway and enhanced cancer cell cycle progression by degrading CDK10 in THCA cells. CONCLUSION: RNF115 triggers cell proliferation, EMT, and tumor metastasis by ubiquitinating and degrading CDK10. The regulation of the Raf-1 pathway and cell cycle progression in THCA may be profoundly influenced by this process.

FaceScape: 3D Facial Dataset and Benchmark for Single-View 3D Face Reconstruction.

In this article, we present a large-scale detailed 3D face dataset, FaceScape, and the corresponding benchmark to evaluate single-view facial 3D reconstruction. By training on FaceScape data, a novel algorithm is proposed to predict elaborate riggable 3D face models from a single image input. FaceScape dataset releases 16,940 textured 3D faces, captured from 847 subjects and each with 20 specific expressions. The 3D models contain the pore-level facial geometry that is also processed to be topologically uniform. These fine 3D facial models can be represented as a 3D morphable model for coarse shapes and displacement maps for detailed geometry. Taking advantage of the large-scale and high-accuracy dataset, a novel algorithm is further proposed to learn the expression-specific dynamic details using a deep neural network. The learned relationship serves as the foundation of our 3D face prediction system from a single image input. Different from most previous methods, our predicted 3D models are riggable with highly detailed geometry under different expressions. We also use FaceScape data to generate the in-the-wild and in-the-lab benchmark to evaluate recent methods of single-view face reconstruction. The accuracy is reported and analyzed on the dimensions of camera pose and focal length, which provides a faithful and comprehensive evaluation and reveals new challenges. The unprecedented dataset, benchmark, and code have been released to the public for research purpose.

LncRNA TRG-AS1 inhibits bone metastasis of breast cancer by the miR-877-5p/WISP2 axis.

TRG-AS1 has been proved to inhibit cancer progression, whereas its effect on bone metastases of breast cancer is unknown. In this study, we determined breast cancer patients with disease free survival is longer in breast cancer patients with high TRG-AS1 expression. Moreover, TRG-AS1 was downregulated in breast cancer tissues and even lower in bone metastatic tumor tissues. Compared with parental breast cancer cell MDA-MB-231, TRG-AS1 expression was downregulated in MDA-MB-231-BO cells with strong bone-metastatic characteristics. Next, the binding sites of miR-877-5p on TRG-AS1 and WISP2 mRNA were predicted and result showed that miR-877-5p could bind to 3'UTR of TRG-AS1 and WISP2. Subsequently, BMMs and MC3T3-E1 cells were cultured in the conditioned media of MDA-MB-231 BO cells transfected with TRG-AS1 overexpression vector, shRNA and/or miR-877-5p mimics or inhibitor and/or overexpression vector and small interfering RNA of WISP2. TRG-AS1 silencing or miR-877-5p overexpression promoted MDA-MB-231 BO cell proliferation and invasion. TRG-AS1 overexpressing reduced TRAP positive cells, decreased TRAP, Cathepsin K, c-Fos, NFATc1 and AREG expression in BMMs, and promoted OPG, Runx2 and Bglap2 expression, and decreased RANKL expression in MC3T3-E1 cells. Silencing WISP2 rescued the effect of TRG-AS1 on BMMs and MC3T3-E1 cells. In vivo results showed that tumor volumes significantly decreased in mice injected with LV-TRG-AS1 transfected MDA-MB-231 cells. TRG-AS1 knockdown markedly reduced the number of TRAP+ cells and the percentage of Ki-67+ cells and decreased E-cadherin expression in xenograft tumor mice. In summary, TRG-AS1 acts an endogenous RNA, inhibited breast cancer bone metastasis by competitively binding with miR-877-5p to upregulate WISP2 expression.

Downregulation of microR-147b represses the proliferation and invasion of thyroid carcinoma cells by inhibiting Wnt/ß-catenin signaling via targeting SOX15.

microRNA-147b (miR-147b) is a newly identified tumor-related miRNA that is dysregulated in multiple cancer types. Yet, the role of miR-147b in thyroid carcinoma remains unknown. Herein, we found that miR-147b expression was upregulated in thyroid carcinoma tissues and cell lines. miR-147b inhibition decreased the proliferation, colony formation, and invasion of thyroid carcinoma cells. The tumor suppressive gene SRY-related high-mobility-group box gene 15 (SOX15) was predicted as a miR-147b target gene. SOX15 expression was markedly decreased in thyroid carcinoma tissues and inversely correlated with the miR-147b expression. SOX15 overexpression repressed the proliferation and invasion of thyroid carcinoma cells associated with downregulation of Wnt/ß-catenin signaling. SOX15 knockdown abolished the miR-147b-inhibition-mediated antitumor effect. miR-147b inhibition or SOX15 overexpression retarded the tumor growth of thyroid carcinoma cells in vivo. Overall, our study suggests that miR-147b inhibition restrains the proliferation and invasion of thyroid carcinoma cells through upregulation of SOX15 and inhibition of Wnt/ß-catenin signaling.