NSCLC TGF Beta

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. SMAD family member 2 (SMAD2) is a key element downstream of the transforming growth factor beta (TGF-β) signaling pathway that regulates cancer metastasis by promoting the epithelial-mesenchyme transition (EMT). MicroRNA miR-486-5p is a tumor suppressor in NSCLC progression. However, it remains unclear whether miR-486-5p is implicated in TGF-β signaling and EMT in NSCLC. In the present study, high expression of SMAD2 mRNA was detected in NSCLC tissues and cell lines, and was associated with poor survival of patients with NSCLC...

Introduction: Accumulating evidence showed that a large number of microRNAs (miRNAs) are abnormally expressed in lung cancer tissues and play critical roles in cancer development and progression. The aim of this study is to identify the differentially expressed miRNAs (DEMs) between non-small cell lung cancer (NSCLC) and normal lung tissues, and evaluate the prognostic value and potential target gene functional enrichment of the DEMs. Materials and Methods: We first downloaded the high-throughput miRNA data from The Cancer Genome Atlas Project (TCGA) database, and subsequently analyzed the data using bioinformatics analysis including limma package in R, Kaplan-Meier curve and Log-rank method, and several online analysis tools...

The role of transforming growth factor beta (TGF-β) in lung cancer is well known. TGF-β-mediated cellular proliferation and angiogenesis through similar to mothers against decapentaplegic homolog 2 (Smad2) protein has also been well elucidated. Smad2 is a predicted target for a microRNAs, namely miR-433. microRNAs are a significant class of non-coding RNAs which play an important role in epigenetic regulation. Here, we show that miR-433 directly binds to Smad2, which is shown to be upregulated in non-small cell lung carcinomas (NSCLC)...

BACKGROUND: Lung cancer is the most important cause of cancer-related deaths worldwide and the overall survival of patients with non-small cell lung cancer has not improved. Transforming growth factor beta or TGF-β is a polypeptide member of the transforming growth factor beta superfamily of cytokines, while far fewer clinical studies addressing the association between TGF-β expression and the disease prognosis have been reported up to now. Therefore, our meta-analysis aims to determine the prognostic significance of TGF-β expression in lung cancer patients...

Purpose : Smoking is a strong relative risk factor for lung cancer. Extracellular vesicles (EVs), particularly exosomes, have been implicated in cancers. In this study, we characterized smoking induced extracellular vesicles in smokers with non-small cell lung cancer (NSCLC). Methods : EVs were isolated from bronchoalveolar lavage (BAL) from smokers and NSCLC patients. EV microRNAs (miRNAs) were analyzed by using a TaqMan microRNA assays. Vesicle mRNAs and long non-coding RNAs (lncRNAs) were measured with quantitative RT-PCR...

BACKGROUND Postoperative recurrence of cancers is responsible for a large portion of deaths in cancer patients. Our study investigated the involvement of lncRNA AWPPH in recurrence of resected non-small cell lung cancer (NSCLC). MATERIAL AND METHODS A total of 128 patients were followed up for 3 years. Blood was extracted from each patient on the day of discharge, the day of the diagnosis of recurrence, or at the end of follow-up. Blood from 30 healthy controls was used as a control group. Patient were divided into 3 groups - a non-recurrence group (NR, n=54), a local recurrence group (LR, n=42), and a distant recurrence (DR, n=32) group - according to the follow-up results...

Diacylglycerol (DAG)/phorbol ester-regulated protein kinase C (PKC) isozymes have been widely linked to tumor promotion and the development of a metastatic phenotype. PKCε, an oncogenic member of the PKC family, is abnormally overexpressed in lung cancer and other cancer types. This kinase plays significant roles in proliferation, survival, and migration; however, its role in epithelial-to-mesenchymal transition (EMT) has been scarcely studied. Silencing experiments in non-small lung cancer (NSCLC) cells revealed that PKCε or other DAG-regulated PKCs (PKCα and PKCδ) were dispensable for the acquisition of a mesenchymal phenotype induced by transforming growth factor beta (TGF-β)...

Garcinol, a dietary factor obtained from Garcinia indica , modulates several key cellular signaling pathways as well as the expression of miRNAs. Acquired resistance to standard therapies, such as erlotinib and cisplatin, is a hallmark of non-small cell lung cancer (NSCLC) cells that often involves miRNA-regulated epithelial-to-mesenchymal transition (EMT). We used A549 cells that were exposed to transforming growth factor beta 1 (TGF-β1), resulting in A549M cells with mesenchymal and drug resistant phenotype, and report that garcinol sensitized resistant cells with mesenchymal phenotype to erlotinib as well as cisplatin with significant decrease in their IC50 values...

BACKGROUND: Tumor-associated macrophage (TAM) is emerging as one of the important complications in cancer promotion. Interleukin-17 (IL-17), a potent pro-inflammatory cytokine, plays an active role in promoting M2 macrophage differentiation (TAMs are M2-like phenotypes). In this study, we aimed to evaluate that IL-17 stimulates key phenotypic and functional signatures of M2 macrophages associated with cancer progression in non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: The markers and cytokines of M2 macrophages were detected in THP-1-derived macrophages and mouse peritoneal macrophages treated with IL-17...

Background: Due to high metastasis and recurrence rate. Recent studies indicated that epithelial-to-mesenchymal transition (EMT) was involved in the progression and metastasis in cancer. Some reports also indicate that HS3ST3B1 played a role in angiogenesis and the proliferation of cancer cells. In this study, we aim to investigate its role in non-small cell lung cancer (NSCLC) . Materials and Methods: All cell lines were purchased from ATCC and cultured in our central lab...

The epithelial-to-mesenchymal transition (EMT) is a crucial event during non-small-cell lung cancer (NSCLC) invasion and metastasis. However, the mechanisms involved in NSCLC EMT have not been fully clarified. Hepatocyte growth factor (HGF) and human biliverdin reductase (hBVR) are reported to contribute to EMT in several diseases. Here, we show that compared with transforming growth factor beta (TGF-β), fibroblast growth factor (FGF), and epidermal growth factor (EGF), HGF is an important cell factor for EMT in NSCLC cell lines A549 and H460...

OBJECTIVE: Epithelial-mesenchymal transition (EMT) is a crucial driver of tumor progression. Tumor growth factor-beta 1 (TGF-β1) is an important factor in EMT induction in tumorigenesis. The targeting of EMT may, therefore, represent a promising approach in anticancer treatment. METHODS: In this study, we determined the effect of decitabine, a DNA methyltransferase inhibitor, on TGF-β1-induced EMT in non-small-cell lung cancer (NSCLC) PC9 and A549 cells. We also assessed the involvement of the miR-200/ZEB axis...

MicroRNA (miR)-9 plays different roles in different cancer types. Here, we investigated the role of miR-9 in non-small-cell lung cancer (NSCLC) cell invasion and adhesion in vitro and explored whether miR-9 was involved in transforming growth factor-beta 1 (TGF-β1)-induced NSCLC cell invasion and adhesion by targeting SOX7. The expression of miR-9 and SOX7 in human NSCLC tissues and cell lines was examined by reverse transcription-quantitative polymerase chain reaction. Gain-of-function and loss-of-function experiments were performed on A549 and HCC827 cells to investigate the effect of miR-9 and SOX7 on NSCLC cell invasion and adhesion in the presence or absence of TGF-β1...

INTRODUCTION: Chronic respiratory conditions, especially chronic obstructive pulmonary disease (COPD), and inflammatory events underlie lung cancer (LC). We hypothesized that profiles of T helper 1 and T helper 2 cytokines and type 1 and type 2 macrophages (M1 and M2) are differentially expressed in lung tumors and blood of patients with NSCLC with and without COPD and that the ratio M1/M2 specifically may influence their survival. METHODS: In blood, inflammatory cytokines (determined by enzyme-linked immunosorbent assay) were quantified in 80 patients with LC (60 with LC and COPD [the LC-COPD group] and 20 with LC only [the LC-only group]) and lung specimens (tumor and nontumor) from those undergoing thoracotomy (20 in the LC-COPD group and 20 in the LC-only group)...

A recent multicenter study led by our institution demonstrated that local recurrence of non-small cell lung cancer (NSCLC) was significantly more frequent in patients with diabetes, raising the possibility of different tumor biology in diabetics. Epithelial-to-mesenchymal transition (EMT) plays a key role in local tumor recurrence and metastasis. In the present study, we investigated differences of tumor microenvironment between patients with and without diabetes by examining expression of EMT markers. Seventy-nine NSCLC patients were selected from the cohort of our early multicenter study...

PURPOSE OF THE STUDY: Confluence-dependent resistance (CDR) is a phenomenon in which the efficacy of anti-cancer agents decreases when cell density increases. CDR in lung cancer has never been reported. The purpose of this study is to investigate if CDR can occur in NSCLC cells and to find a role for transforming growth factor (TGF)-β as a mechanism of CDR. MATERIALS AND METHODS: Non-small cell lung cancer (NSCLC) cell lines A549 and H2228 were exposed to cisplatin in a variety of cell density conditions...

A deeper understanding of the key role of the immune system in regulating tumor growth and progression has led to the development of a number of immunotherapies, including cancer vaccines and immune checkpoint inhibitors. Immune checkpoint inhibitors target molecular pathways involved in immunosuppression, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway, with the goal to enhance the host's own immune anticancer response...

BACKGROUND: The transforming growth factor-beta (TGF- β) pathway has been implicated in proliferation, migration and invasion of various cancers. Endoglin is a TGF-β accessory receptor that modulates signalling. We identified Endoglin as an epigenetically silenced tumour-suppressor gene in lung cancer by means of a genome-wide screening approach, then sought to characterise its effect on lung cancer progression. METHODS: Methylation microarray and RNA sequencing were carried out on lung cancer cell lines...

The fine balance of T help-17 (Th17)/regulatory T(Treg) cells is crucial for maintenance of immune homeostasis. However, there is little information concerning the role played in non-small cell lung cancer (NSCLC) by Th17/Treg cells. The objective of this study was to investigate the variation of Th17 and Treg cells in the peripheral blood of patients with NSCLC. Blood samples were collected from 19 patients with NSCLC and 19 healthy donors. Samples were processed to detect CD4(+)IL-17(+) Th17 cells and CD4(+)CD25(+)Foxp3(+) Treg cells by flow cytometry, and related gene expressions were assessed by real-time quantitative polymerase chain reaction...

UNLABELLED: The eIF3e protein is a component of the multisubunit eIF3 complex, which is essential for cap-dependent translation initiation. Decreased eIF3e expression is often observed in breast and lung cancer and has been shown to induce epithelial-to-mesenchymal transition (EMT) in breast epithelial cells by an unknown mechanism. Here, we study the effect of decreased eIF3e expression in lung epithelial cells by creating stable clones of lung epithelial cells (A549) that express an eIF3e-targeting shRNA...