Expression of cross-tolerance to a wide range of conditions in a human lung cancer cell line after adaptation to nitric oxide.

Previously, we have shown that A549, a human lung adenocarcinoma, can be adapted to nitric oxide (NO). NO is a nitrogen-based free radical that is synthesized by a family of enzymes known as nitric oxide synthases. NO has been shown to be overexpressed in patient populations of different cancers.

Transcriptomic Analysis of mRNAs in Human Monocytic Cells Expressing the HIV-1 Nef Protein and Their Exosomes.

The Nef protein of human immunodeficiency virus (HIV) promotes viral replication and progression to AIDS. Besides its well-studied effects on intracellular signaling, Nef also functions through its secretion in exosomes, which are nanovesicles containing proteins, microRNAs, and mRNAs and are important for intercellular communication. Nef expression enhances exosome secretion and these exosomes can enter uninfected CD4 T cells leading to apoptotic death.

A549 cells adapted to high nitric oxide show reduced surface CEACAM expression and altered adhesion and migration properties.

The migration and adhesion properties of tumors affect their metastatic rate. In the present study, we investigated carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 1, 5, and 6 expression in high nitric oxide (HNO)-adapted lung cancer cells compared to parent cells. We observed high transcript levels of CEACAM 1 (4S, 4L), CEACAM 5, and CEACAM 6 in HNO cells compared to parent cells.

The HIV Nef protein modulates cellular and exosomal miRNA profiles in human monocytic cells.

Introduction: The HIV Nef protein is a multifunctional virulence factor that perturbs intracellular membranes and signalling and is secreted into exosomes. While Nef-containing exosomes have a distinct proteomic profile, no comprehensive analysis of their miRNA cargo has been carried out. Since Nef functions as a viral suppressor of RNA interference and disturbs the distribution of RNA-induced silencing complex proteins between cells and exosomes, we hypothesized that it might also affect the export of miRNAs into exosomes.

Part II-mechanism of adaptation: A549 cells adapt to high concentration of nitric oxide through bypass of cell cycle checkpoints.

Previous work has shown enhanced survival capacity in high nitric oxide (HNO)-adapted tumor cells. In Part I of this series of manuscripts, we have shown that A549-HNO cells demonstrate an improved growth profile under UV and X-ray radiation treatment. These cells exhibit increased expression of proteins involved in DNA damage recognition and repair pathway, both the non-homologous end joining pathway and homologous recombination.

Part I-mechanism of adaptation: high nitric oxide adapted A549 cells show enhanced DNA damage response and activation of antiapoptotic pathways.

Our previous studies demonstrate that A549, a human lung adenocarcinoma line, could be adapted to the free radical nitric oxide (NO([Symbol: see text])). NO([Symbol: see text]) has been shown to be overexpressed in human tumors. The original cell line, A549 (parent), and the newly adapted A549-HNO (which has a more aggressive phenotype) serves as a useful model system to study the role of NO([Symbol: see text]) in tumor biology.

The HIV-1 Nef protein binds argonaute-2 and functions as a viral suppressor of RNA interference.

The HIV-1 accessory protein Nef is an important virulence factor. It associates with cellular membranes and modulates the endocytic machinery and signaling pathways. Nef also increases the proliferation of multivesicular bodies (MVBs), which are sites for virus assembly and budding in macrophages.