Network analysis reveals essential proteins that regulate sodium-iodide symporter expression in anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is the most rare and lethal form of thyroid cancer and requires effective treatment. Efforts have been made to restore sodium-iodide symporter (NIS) expression in ATC cells where it has been downregulated, yet without complete success. Systems biology approaches have been used to simplify complex biological networks. Here, we attempt to find more suitable targets in order to restore NIS expression in ATC cells. We have built a simplified protein interaction network including transcription factors and proteins involved in MAPK, TGFß/SMAD, PI3K/AKT, and TSHR signaling pathways which regulate NIS expression, alongside proteins interacting with them. The network was analyzed, and proteins were ranked based on several centrality indices. Our results suggest that the protein interaction network of NIS expression regulation is modular, and distance-based and information-flow-based centrality indices may be better predictors of important proteins in such networks. We propose that the high-ranked proteins found in our analysis are expected to be more promising targets in attempts to restore NIS expression in ATC cells.

Mitochondrial delivery of microRNA mimic let-7b to NSCLC cells by PAMAM-based nanoparticles.

Many biological mechanisms including cellular metabolism and cell death are regulated by mitochondria known as powerhouse of the cell. Recently, let-7b, a tumour-suppressor microRNA has been detected in mitochondria of human cells targeting several mitochondrial-encoded respiratory chain genes. Triphenylphosphonium cation (TPP) is one of the major classes of mitochondriotropics that possess the ability of specifically targeting the mitochondria. PAMAM dendrimers are one of the most available agents in gene delivery due to their well-defined and beneficial features such as large density of surface functional groups. Hyaluronic acid (HA), a natural polysaccharide has been demonstrated to have the abilities such as good biocompatibility and targeting CD44 overexpressed receptors on non-small cell lung cancer (NSCLC) cells. In this research, let-7b-PAMAM (G5)-TPP and let-7b-PAMAM (G5)-TPP-HA nano-carriers were designed to deliver let-7b miRNA mimic to NSCLC cells' mitochondria as a novel way of cancer cells inhibition. Nano-carriers were capable of being successfully taken up by A549 cells and localised in mitochondria environment. Let-7b loaded nanoparticles reduced cell viability and induced apoptosis significantly. Expression of genes involved in mitochondrial oxidative function was decreased resulting in nanoparticles effect on mitochondria. Application of mitochondria targeted-miRNA delivery systems could regulate cellular functions to inhibit lung cancer.