Project description:Several long non-coding RNAs (lncRNAs) are differentially expressed in oral cancer, contributing to Oral squamous cell carcinoma (OSCC), an aggressive cancer of the head and neck region. A dysregulated Transforming growth factor-beta (TGF-β) pathway is often observed in OSCC, leading to increased proliferation, migration, invasion, and chemoresistance in OSCC cells. The role of TGF-β regulated lncRNAs in promoting malignancy has already been established in multiple cancers. Such differentially expressed lncRNA involved in cross-talks with the TGF-β pathway is also reported in OSCC. We suspect many such lncRNAs function downstream of the TGF-β pathway in OSCC. We use whole transcriptomic sequencing to identify lncRNAs which are induced upon TGF-β treatment in OSCC via SMAD dependent or SMAD independent pathways to promote OSCC pathogenesis.
Project description:We have previously demonstrated that TNF-α, a proinflammatory cytokine, enhances TGF-β-mediated EMT in A549 human lung cancer cells. RNA-sequencing analysis on CMT64 cells following TGF-β and/or TNF-α treatment revealed a subset of genes possibly regulated by TGF-β and/or TNF-α.
Project description:Recent studies demonstrate that Ca2+ signaling has an important role in EMT. Use of Ca2+ blockers such as 2APB can inhibit cell migration induced by TGF-β. Interestingly, we see an unexpected increase in Snail expression upon Ca2+ blocker treatment of both MCF10A and NMuMG cells; this increase is not observed with 2APB treatment alone. Therefore, we believe that 2APB plays a synergistic role with TGF-β in Snail induction. We propose to investigate the gene networks that change following 2APB +TGF-β treatment.
Project description:Advanced ovarian cancer is the most lethal gynecologic malignancy in the United States. Ovarian cancer cells are known to have diminished response to TGF-beta, but it remains unclear whether TGF-beta can modulate ovarian cancer cell growth in an indirect manner through cancer-associated fibroblasts (CAFs). Using transcriptome profiling analyses on TGF-beta-treated ovarian fibroblasts, we identified a TGF-beta-responsive gene signature in ovarian fibroblasts. Identifying TGF-beta-regulated genes in the ovarian microenvironment helps in understanding the role of TGF-beta in ovarian cancer progression. The human telomerase-immortalized ovarian fibroblast line NOF151 was treated with 5ng/mL of either TGF-beta-1 or TGF-beta-2. Total RNA was isolated from control samples and TGF-beta-treated fibroblasts samples at 48 hours post-treatment, followed by cDNA synthesis, IVT and biotin labeling. Samples were then hybridized onto Affymetrix Human Genome U133 Plus 2.0 microarrays. For each treatment group, three independent samples were prepared for the microarray experiment.
Project description:Growth factor, TGF beta can have profound effect on global gene expression changes. Since TGF beta signalling is not well studied in liver epithelia , we decided to do Next gen RNA-seq analysis to look at TGF beta signaling in cholangiocytes
Project description:Very little is known about how intervertebral disc (IVD) is formed or maintained. Members of the TGF-beta superfamily are secreted signaling proteins that regulate many aspects of development including cellular differentiation. We recently showed that deletion of Tgfbr2 in Col2a expressing tissue results in alterations in development of IVD annulus fibrosus. The results suggested TGF-beta has an important role in regulating development of the axial skeleton, however, the mechanistic basis of TGF-beta action in these specialized joints is not known. To understand the mechanism of TGF-beta action in IVD development, we undertook a global analysis of gene expression comparing gene expression profiles in sclerotome cultures treated with TGF-beta or BMP4. As expected, treatment with BMP4 resulted in up-regulation of cartilage marker genes including Acan, Sox 5, Sox6, and Sox9. In contrast, treatment with TGF-beta1 did not regulate expression of cartilage markers but instead resulted in up-regulation of many IVD markers including Fmod and Adamtsl2. We propose TGF-beta has two functions in IVD development: 1) to prevent chondrocyte differentiation in the presumptive IVD and 2) to promote differentiation of annulus fibrosus from sclerotome. We have identified genes that are enriched in the IVD and regulated by TGF-beta that warrant further investigation as regulators of IVD development. Nine samples were analyzed. Three biological replicates of untreated sclerotome grown in micromass culture. Three biological replicates of cells treated with 50 ng/ml BMP4 for 8 hours and three biological replicates of cells treated with 5 ng/ ml TGF-beta1 for 8 hours.