Guang Chen

Nuclear localization of the androgen receptor (AR) is necessary for its activation as a transcription factor. Defining the mechanisms regulating AR nuclear localization in androgen-sensitive cells and how these mechanisms are dysregulated in castration-resistant prostate cancer (CRPC) cells is fundamentally important and clinically relevant. According to the classical model of AR intracellular trafficking, androgens induce AR nuclear import and androgen withdrawal causes AR nuclear export. The present study has led to an updated model that AR could be imported in the absence of androgens, ubiquitinated, and degraded in the nucleus. Androgen withdrawal caused nuclear AR degradation, but not export. In comparison with their parental androgen-sensitive LNCaP prostate cancer cells, castration-resistant C4-2 cells exhibited reduced nuclear AR polyubiquitination and increased nuclear AR level. We previously identified 3-(4-chlorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (CPPI) in a high-throughput screen for its inhibition of androgen-independent AR nuclear localization in CRPC cells. The current study shows that CPPI is a competitive AR antagonist capable of enhancing AR interaction with its E3 ligase MDM2 and degradation of AR in the nuclei of CRPC cells. Also, CPPI blocked androgen-independent AR nuclear import. Overall, these findings suggest the feasibility of targeting androgen-independent AR nuclear import and stabilization, two necessary steps leading to AR nuclear localization and activation in CRPC cells, with small molecule inhibitors.

Statement of Retraction We, the Editors and Publisher of the journal Cell Cycle, have retracted the following article: Bofan Yu, Wei You, Guang Chen, Yang Yu, and Qinheng Yang. MiR-140-5p inhibits cell proliferation and metastasis by regulating MUC1 via BCL2A1/ MAPK pathway in triple negative breast cancer. Cell Cycle. 2019;18(20):2641–2650. doi: 10.1080/15384101.2019.1653107 Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address all the concerns raised and have not been able to provide all their original data. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. The authors have agreed to retract the article. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Intervertebral disc (IVD) degeneration is a pathological process, which may lead to lower back pain. The present study aimed to investigate the pathogenesis of IVD degeneration. GSE42611 was downloaded from Gene Expression Omnibus, including 4 nucleus pulposus samples isolated from degenerated IVDs and 4 nucleus pulposus samples separated from normal IVDs. The differentially expressed genes (DEGs) between the degenerated and normal samples were screened using the limma package in R. Functional and pathway enrichment analyses were conducted separately for the upregulated and downregulated genes, using Database for Annotation, Visualization and Integrated Discovery software. In addition, protein‑protein interaction (PPI) networks were constructed using the Search Tool for the Retrieval of Interacting Genes database and Cytoscape software. Finally, module analyses were conducted for the PPI networks using the MCODE plug‑in in Cytoscape. A total of 558 DEGs were identified in the degenerated nucleus pulposus cells: 253 upregulated and 305 downregulated. Pathway enrichment analysis revealed that downregulated thrombospondin 1 (THBS1) was enriched in extracellular matrix‑receptor interaction. Interleukin (IL)‑6 in the PPI network for the upregulated genes and vascular endothelial growth factor A (VEGFA) in the PPI network for the downregulated genes had higher degrees. Additionally, four modules (µM1, µM2, µM3 and µM4) were identified from the PPI network for the upregulated genes. Four modules (dM1, dM2, dM3 and dM4) were identified from the PPI network for the downregulated genes. In the dM2 module, collagen genes and integrin subunit α4 (ITGA4) may interact with each other. Additionally, functional enrichment indicated that collagen genes were enriched in extracellular matrix organization. In conclusion, IL‑6, VEGFA, THBS1, ITGA4 and collagen genes may contribute to the progression of IVD degeneration. These results suggested that the manipulation of these genes and their products may have potential as a novel therapeutic strategy for the treatment of patients with IVD.

OBJECTIVE: This study was to explore the effects of RNA interference mediated vascular endothelial growth factor (VEGF ) gene silencing on biological behavior of renal cell carcinoma (RCC), transplanted renal tumor and angiogenesis in nude mice. METH

An image-based immersive tool is proposed to diagnose the severity of the dementia disease based on arterial spin labeling images for the first time in this paper. A Gaussian form of mahalanobis distance is incorporated to measure the pair-wise similarity of images, and its with-in full matrix is automatically determined via spectral clustering and incremental learning techniques. There are totally 350 demented patients belonging to three groups, i.e., Alzheimer's disease, mild cognitive impairment, and non cognitive impairment, utilized for experimental evaluation. Several other methods are also implemented and compared with the newly proposed method from the statistical perspective. It is concluded that the new method outperforms others in this dementia diagnosis study.