Increased expression of microRNA-155-5p by alveolar type II cells contributes to development of lethal ARDS in H1N1 influenza A virus-infected mice.

Alveolar type II (ATII) cells are essential to lung function and a primary site of influenza A virus (IAV) replication. Effects of IAV infection on ATII cell microRNA (miR) expression have not been comprehensively investigated. Infection of C57BL/6 mice with 10,000 or 100 pfu/mouse of IAV A/WSN/33 (H1N1) significantly altered expression of 73 out of 1908 mature murine miRs in ATII cells at 2 days post-infection (d.

ncRNA Editing: Functional Characterization and Computational Resources.

Noncoding RNAs (ncRNAs) have received much attention due to their central role in gene expression and translational regulation as well as due to their involvement in several biological processes and disease development. Small noncoding RNAs (sncRNAs), such as microRNAs and piwiRNAs, have been thoroughly investigated and functionally characterized. Long noncoding RNAs (lncRNAs), known to play an important role in chromatin-interacting transcription regulation, posttranscriptional regulation, cell-to-cell signaling, and protein regulation, are also being investigated to further elucidate their functional roles.

RNA Methylation in ncRNA: Classes, Detection, and Molecular Associations.

Nearly all classes of coding and non-coding RNA undergo post-transcriptional modification, as more than 150 distinct modification types have been reported. Since RNA modifications were first described over 50 years ago, our understanding of their functional relevance in cellular control mechanisms and phenotypes has truly progressed only in the last 15 years due to advancements in detection and experimental techniques. Specifically, the phenomenon of RNA methylation in the context of ncRNA has emerged as a novel process in the arena of epitranscriptomics.

Extracellular miRNAs as biomarkers in cancer.

Cancer is the leading cause of death worldwide. Despite significant progress in the field leading to identification of molecular signatures of individual tumors and the development of targeted therapies, early cancer diagnosis remains a clinical challenge. The emerging era of personalized medicine has intensified research towards biomarkers that can be obtained via noninvasive means.

Rad51C-ATXN7 fusion gene expression in colorectal tumors.

Background: Fusion proteins have unique oncogenic properties and their identification can be useful either as diagnostic or therapeutic targets. Next generation sequencing data have previously shown a fusion gene formed between Rad51C and ATXN7 genes in the MCF7 breast cancer cell line. However, the existence of this fusion gene in colorectal patient tumor tissues is largely still unknown.

Stromal Caveolin-1 Is Associated With Response and Survival in a Phase II Trial of nab-Paclitaxel With Carboplatin for Advanced NSCLC Patients.

Unlabelled: In this phase II trial, carboplatin with nanoparticle albumin-bound (nab)-paclitaxel as first-line therapy for advanced non-small-cell lung cancer (NSCLC) was evaluated. Most patients had squamous cell histology. Tumor-associated stromal caveolin-1 (Cav-1) expression was correlated with improved response rate and survival in NSCLC patients who received nab-paclitaxel in this phase II trial.

A middle-aged man presenting with unexplained mucosal erosions and progressive dyspnoea.

Paraneoplastic pemphigus (PNP) is a rare syndrome driven by antibodies (IgG) binding to desmogleins and other epidermal proteins leading to skin erosions. In rare instances, these same IgG proteins may also target the bronchial mucosa leading to an irreversible fibrotic reaction within the epithelium and subsequent obstructive lung disease. A 51-year-old man presented to the emergency department with 2-3-month history of dyspnoea as well as oral and genital ulcerations and inguinal lymphadenopathy.

MicroRNA as tools and therapeutics in lung cancer.

Lung cancer is the number one cause of cancer related deaths. The lack of specific and accurate tools for early diagnosis and minimal targeted therapeutics both contribute to poor outcomes. The recent discovery of microRNAs (miRNAs) revealed a novel mechanism for post-transcriptional regulation in cancer and has created new opportunities for the development of diagnostics, prognostics and targeted therapeutics.

Selective targeting of alveolar type II respiratory epithelial cells by anti-surfactant protein-C antibody-conjugated lipoplexes.

Alveolar type II (ATII) respiratory epithelial cells are essential to normal lung function. They may be also central to the pathogenesis of diseases such as acute lung injury, pulmonary fibrosis, and pulmonary adenocarcinoma. Hence, ATII cells are important therapeutic targets.

MicroRNA regulation of tumorigenesis, cancer progression and interpatient heterogeneity: towards clinical use.

In the past two decades, microRNAs have emerged as crucial mediators of organ development and human disease. Here, we discuss their role as drivers or suppressors of the hallmarks of cancer during tumorigenesis and progression, in defining interpatient heterogeneity and the promise of therapeutic application.

MicroRNAs in respiratory disease. A clinician's overview.

Since their initial discovery in the early 1990s, microRNAs have now become the focus of a multitude of lines of investigation ranging from basic biology to translational applications in the clinic. Previously believed to be of no biological relevance, microRNAs regulate processes fundamental to human health and disease. In diseases of the lung, microRNAs have been implicated in developmental programming, as drivers of disease, potential therapeutic targets, and clinical biomarkers; however, several obstacles must be overcome for us to fully realize their potential therapeutic use.

Detection of extracellular RNAs in cancer and viral infection via tethered cationic lipoplex nanoparticles containing molecular beacons.

Noninvasive early detection methods have the potential to reduce mortality rates of both cancer and infectious diseases. Here, we present a novel assay by which tethered cationic lipoplex nanoparticles containing molecular beacons (MBs) can capture cancer cell-derived exosomes or viruses and identify encapsulated RNAs in a single step. A series of ultracentrifugation and Exoquick isolation kit were first used to isolate exosomes from the cell culture medium and human serum, respectively.

Molecular biology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

Based on recent bench and clinical research, the treatment of lung cancer has been refined, with treatments allocated according to histology and specific molecular features. For example, targeting mutations such as epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors has been particularly successful as a treatment modality, demonstrating response rates in selected patients with adenocarcinoma tumors harboring EGFR mutations that are significantly higher than those for conventional chemotherapy. However, the development of new targeted therapies is, in part, highly dependent on an improved understanding of the molecular underpinnings of tumor initiation and progression, knowledge of the role of molecular aberrations in disease progression, and the development of highly reproducible platforms for high-throughput biomarker discovery and testing.

Therapeutic Delivery of MicroRNA-29b by Cationic Lipoplexes for Lung Cancer.

MicroRNA-29b (miR-29b) expression has been shown to be reduced in non-small-cell lung cancer (NSCLC) tissues. Here, we have identified the oncogene cyclin-dependent protein kinase 6 (CDK6) as a direct target of miR-29b in lung cancer. We hypothesized that in vivo restoration of miR-29b and thus targeting of genes important to tumor initiation and progression may represent an option for lung cancer treatment.

Surface-mediated nucleic acid delivery by lipoplexes prepared in microwell arrays.

Many delivery methods have been developed to improve the therapeutic efficacy and facilitate the clinical translation of nucleic acid-based therapeutics. A facile surface-mediated nucleic acid delivery by lipoplexes is prepared in a microwell array, which combines the advantages of lipoplexes as an efficient carrier system, surface-mediated delivery, and the control of surface topography. Uniform disc-like lipoplexes containing nucleic acids are formed in the microwell array with a diameter of ∼818 nm and thickness of ∼195 nm.

A mathematical model for microRNA in lung cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide. Lack of early detection and limited options for targeted therapies are both contributing factors to the dismal statistics observed in lung cancer. Thus, advances in both of these areas are likely to lead to improved outcomes.

Epigenetic regulation of miR-17~92 contributes to the pathogenesis of pulmonary fibrosis.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a disease of progressive lung fibrosis with a high mortality rate. In organ repair and remodeling, epigenetic events are important. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and can target epigenetic molecules important in DNA methylation.

MiR-101 and miR-144 regulate the expression of the CFTR chloride channel in the lung.

The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that plays a critical role in the lung by maintaining fluid homeostasis. Absence or malfunction of CFTR leads to Cystic Fibrosis, a disease characterized by chronic infection and inflammation. We recently reported that air pollutants such as cigarette smoke and cadmium negatively regulate the expression of CFTR by affecting several steps in the biogenesis of CFTR protein.

Clinical applications for microRNAs in cancer.

The discovery that noncoding components of the genome, including microRNA (miRNA or miR), can contribute to the pathogenesis of cancer has led investigators to contemplate using these molecules to guide clinical decision making. Currently, miRNA signatures are being applied in human clinical trials and miRNA-directed therapy is under way, with miR-122 targeting in hepatitis C (HCV) being the most developed therapy thus far. miRNA-based targeting in cancer is not far behind, with several private companies developing therapeutics.