No abstract

Breast cancer is a heterogeneous disease characterized by multiple genetic alterations leading to the activation of growth factor signaling pathways that promote cell proliferation. Platelet-derived growth factor-C (PDGF-C) is overexpressed in various malignancies; however, the involvement of PDGF-C in breast cancers and the mechanisms underlying PDGF-C deregulation remain unclear. Here, we show that PDGF-C is overexpressed in clinical breast cancers and correlates with poor prognosis. PDGF-C up-regulation was mediated by the human embryonic lethal abnormal vision-like protein HuR, which stabilizes the PDGF-C transcript by binding to two predicted AU-rich elements (AREs) in the 3'-untranslated region (3'-UTR). HuR is up-regulated in hydrogen peroxide-treated or ultraviolet-irradiated breast cancer cells. Clinically, HuR levels are correlated with PDGF-C expression and histological grade or pathological tumor-node-metastasis (pTNM) stage. Our OPEN ACCESSInt. J. Mol. Sci. 2014, 15 20307 findings reveal a novel mechanism underlying HuR-mediated breast cancer progression, and suggest that HuR and PDGF-C are potential molecular candidates for targeted therapy of breast cancers.

Hepatic stellate cells (HSCs) are located in the space of Disse, between liver sinusoidal endothelia cells (LSECs) and hepatocytes. They have surprised and excited hepatologists for their biological characteristics. Under physiological quiescent conditions, HSCs are the major vitamin A-storing cells of the liver, playing crucial roles in the liver development, regeneration, and tissue homeostasis. Upon injury-induced activation, HSCs convert to a pro-fibrotic state, producing the excessive extracellular matrix (ECM) and promoting angiogenesis in the liver fibrogenesis. Activated HSCs significantly contribute to liver fibrosis progression and inactivated HSCs are key to liver fibrosis regression. In this review, we summarize the comprehensive understanding of HSCs features, including their roles in normal liver and liver fibrosis in hopes of advancing the development of emerging diagnosis and treatment for hepatic fibrosis.

Aim: Hepatic fibrosis is one of the most common conditions worldwide, and yet no effective antifibrotic therapy is available. This study aimed to reverse hepatic fibrosis via exosome-mediated delivery of the CRISPR/dCas9-SAM system. Materials & methods: The authors constructed a modified-exosome delivery system targeting hepatic stellate cells (HSCs), and constructed the CRISPR/dCas9-SAM system inducing HSCs convert into hepatocyte-like cells in vitro and in vivo. Results: RBP4-modified exosomes could efficiently load and deliver the CRISPR/dCas9 system to HSCs. The in vitro CRISPR/dCas9 system induced the conversion from HSCs to hepatocyte-like cells via targeted activation of HNF4α/ HGF1/ FOXA2 genes. Importantly, in vivo targeted delivery of this system significantly attenuated CCl4-induced hepatic fibrosis. Conclusion: Targeted activation of HNF4α/ HGF1/ FOXA2 reverses hepatic fibrosis via exosome-mediated delivery of the CRISPR/dCas9-SAM system, which provides a feasible antifibrotic strategy.

Exosomes are small extracellular vesicles that can be secreted by any type of cell, released into almost all biological fluids, and extracted from anybody fluid such as blood, urine, saliva, and amniotic fluid. The theranostic role of exosome in liver diseases has been widely studied in recent years. In this review, we briefly introduce the biological characteristics of exosomes and then focus on the theranostics of exosomes in liver diseases, specifically gene delivery associated with liver diseases.