glioblastoma-relapse-post-resection-model-for-therapeutic-hydrogel

Glioblastoma Relapse Post-Resection Model for Therapeutic Hydrogel Investigations

Tumor recurrence is an important factor indicative of a poor prognosis in glioblastoma (GBM). Many studies are attempting to identify effective ...

Nanjing Medical University

Excessive proliferation and migration of fibroblasts contribute to pulmonary fibrosis in silicosis, and both epithelial cells and endothelial cells participate in the accumulation of fibroblasts via the epithelial-mesenchymal transition (EMT) and the endothelial-mesenchymal transition (EndMT), respectively. A mouse endothelial cell line (MML1) was exposed to silicon dioxide (SiO, 50 μg/cm), and immunofluorescence and western blot analyses were performed to evaluate levels of specific endothelial and mesenchymal markers and to elucidate the mechanisms by which SiO induces the EndMT. Functional changes were evaluated by analyzing cell migration and proliferation. The mRNA and circular RNA (circRNA) levels were measured using qPCR and fluorescent in situ hybridization (FISH). Lung tissue samples from both Tie2-GFP mice exposed to SiO and silicosis patients were applied to confirm the observations from in vitro experiments. Based on the results from the current study, SiO increased the expression of mesenchymal markers (type I collagen (COL1A1), type III collagen (COL3A1) and alpha smooth muscle actin (α-SMA/Acta2)) and decreased the expression of endothelial markers (vascular endothelial cadherin (VE-Cad/Cdh 5) and platelet endothelial cell adhesion molecule-1 (PECAM1)), indicating the occurrence of the EndMT in response to SiO exposure both in vivo and in vitro. SiO concomitantly increased circHECTD1 expression, which, in turn, inhibited HECTD1 protein expression. SiO-induced increases in cell proliferation, migration, and changes in marker levels were restored by either a small interfering RNA (siRNA) targeting circHECTD1 or overexpression of HECTD1 via the CRISPR/Cas9 system, confirming the involvement of the circHECTD1/HECTD1 pathway in the EndMT. Moreover, tissue samples from SiO-exposed mice and silicosis patients confirmed the EndMT and change in HECTD1 expression. Our findings reveal a potentially new function for the circHECTD1/HECTD1 pathway and suggest a possible mechanism of fibrosis in patients with pulmonary silicosis.

circHECTD1 promotes the silica-induced pulmonary endothelial-mesenchymal transition via HECTD1.

The epithelial to mesenchymal transition (EMT) contributes to fibrosis during silicosis. Zinc finger CCCH-type containing 4 protein (ZC3H4) is a novel CCCH-type zinc finger protein that activates inflammation in pulmonary macrophages during silicosis. However, whether ZC3H4 is involved in EMT during silicosis remains unclear. In this study, we investigated the circular ZC3H4 (circZC3H4) RNA/microRNA-212 (miR-212) axis as the upstream molecular mechanism regulating ZC3H4 expression and the downstream mechanism by which ZC3H4 regulates EMT as well as its accompanying migratory characteristics.

The emerging roles of a novel CCCH-type zinc finger protein, ZC3H4, in silica-induced epithelial to mesenchymal transition.

Retinoblastoma (RB) is the most common childhood malignant intraocular tumor. The clinical efficacy of vincristine (VCR) in the treatment of RB is severely limited by drug resistance. Here, we found that CD24, a GPI-anchored protein, was overexpressed in human RB tissues and RB cell lines, and was associated with the sensitivity of RB cells in response to VCR therapy. We demonstrated that CD24 plays a critical role in impairing RB sensitivity to VCR via regulating autophagy. Mechanistically, CD24 recruits PTEN to the lipid raft domain and regulates the PTEN/AKT/mTORC1 pathway to activate autophagy. Lipid raft localization was essential for CD24 recruitment function. Collectively, our findings revealed a novel role of CD24 in regulating RB sensitivity to VCR and showed that CD24 is a potential target for improving chemotherapeutic sensitivity and RB patient outcomes.

CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy.

The significance of the relationship between the microbiota and diseases is increasingly being recognized. However, the characterization of tumor microbiome and their precise molecular mechanisms through which microbiota promotes hepatocellular carcinoma (HCC) development are still unclear.

Hepatic stellate cell activation and senescence induced by intrahepatic microbiota disturbances drive progression of liver cirrhosis toward hepatocellular carcinoma.

Article	Year
circHECTD1 promotes the silica-induced pulmonary endothelial-mesenchymal transition via HECTD1. Cell death & disease\| PubMed ID: 29540674	2018
The emerging roles of a novel CCCH-type zinc finger protein, ZC3H4, in silica-induced epithelial to mesenchymal transition. Toxicology letters\| PubMed ID: 30826420	2019
CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy. Molecular oncology\| PubMed ID: 32394616	2020
Hepatic stellate cell activation and senescence induced by intrahepatic microbiota disturbances drive progression of liver cirrhosis toward hepatocellular carcinoma. Journal for immunotherapy of cancer\| PubMed ID: 34996812	2022

Zewei Zhou

Biography

JoVE Journal Publications

Other Publications