Project description:PURPOSE: To provide a detailed gene expression profile of the normal postnatal mouse cornea. METHODS: Serial analysis of gene expression (SAGE) was performed on postnatal day (PN)9 and adult mouse (6 week) total corneas. The expression of selected genes was analyzed by in situ hybridization. RESULTS: A total of 64,272 PN9 and 62,206 adult tags were sequenced. Mouse corneal transcriptomes are composed of at least 19,544 and 18,509 unique mRNAs, respectively. One third of the unique tags were expressed at both stages, whereas a third was identified exclusively in PN9 or adult corneas. Three hundred thirty-four PN9 and 339 adult tags were enriched more than fivefold over other published nonocular libraries. Abundant transcripts were associated with metabolic functions, redox activities, and barrier integrity. Three members of the Ly-6/uPAR family whose functions are unknown in the cornea constitute more than 1% of the total mRNA. Aquaporin 5, epithelial membrane protein and glutathione-S-transferase (GST) omega-1, and GST alpha-4 mRNAs were preferentially expressed in distinct corneal epithelial layers, providing new markers for stratification. More than 200 tags were differentially expressed, of which 25 mediate transcription. CONCLUSIONS: In addition to providing a detailed profile of expressed genes in the PN9 and mature mouse cornea, the present SAGE data demonstrate dynamic changes in gene expression after eye opening and provide new probes for exploring corneal epithelial cell stratification, development, and function and for exploring the intricate relationship between programmed and environmentally induced gene expression in the cornea. Keywords: other
Project description:MicroRNAs (miRNAs) function as regulators of cancer progression as they modulate different cellular processes. The objective of this study is to demonstrate a multi-dimensional function of miR-30e through regulating genes involved in various signaling pathways including androgen receptor signaling. miR-30e targets androgen receptor mRNA and functions as a tumor suppressor. We noted loss of miR-30e expression in prostate tumors and restored expression of miR-30e led to cell cycle arrest, induction of apoptosis, improved drug sensitivity in prostate cancer cells, and reduced tumor progression in prostate cancer xenograft models. To understand the tumor suppressor function of miR-30e on a global scale, we performed total RNA-sequence analysis upon overexpression of miR-30e in a prostate cancer cell line 22Rv-1, which expresses a splice variant of androgen receptor and represents an androgen-independent and drug-resistant form of prostate cancer.qRT-PCR validation of RNA-sequencing data supports our in vitro study showeing differential expression of genes involved in cell cycle progression, apoptosis and ubiquitination upon expression of miR-30e in prostate cancer cells.
Project description:Aberrant androgen receptor (AR)-mediated transcription is a critical driver in progression of human prostate cancer. It's known that different doses of androgens can elicit differential transcriptional and proliferative responses in prostate-tumor cells. Here, we set out to examine the androgenic regulation of glycoprotein expression in the membrane fraction of prostate-tumor cells that could serve as mediators or markers of androgen-induced proliferative responses observed in prostate-tumor cells. A bioanalytical workflow involving lectin-affinity chromatography and label-free quantitative mass spectrometry was used to identify androgen-sensitive glycomembrane protein expression associated with androgen-mediated proliferation. This study would facilitate the identification of surface membrane proteins involved in androgen-mediated proliferation and provide potential therapeutic targets in the detection treatment of proliferation prostate-tumors.
Project description:We found that BAP1 (BRCA1 Associated Protein-1) shows loss of heterozygosity in over 25% of pancreatic cancer patients and functions as tumor suppressor. Conditional deletion of Bap1 in murine pancreas led to genomic instability, accumulation of DNA damage, and an inflammatory response that evolved to pancreatitis with full penetrance. Concomitant expression of oncogenic KrasG12D led to malignant transformation and development of invasive and metastatic pancreatic cancer. At the molecular level, BAP1 maintains the integrity of the exocrine pancreas by regulating genomic stability and its loss confers sensitivity to radio- and platinum-based therapies.
Project description:Following extensive treatment with androgen receptor (AR) pathway inhibitors, a significant number of metastatic prostate cancer develop treatment resistance, and approximately 20% of these castration-resistant prostate cancers (CRPC) transdifferentiate, at least partially, into neuroendocrine (NE) prostate cancer (NEPC).In human cancer, FOXA2 is highly expressed in most of NEPC and a small portion of CRPC patients, has been suggested as a marker of NEPC and elevated in other NE lineage cancers including SCLC. In addition, preclinical studies demonstrated that Foxa2 is required for NEPC tumor growth and metastasis in TRAMP mouse model and associated with NEPC transformation in Pten, Trp53, and Rb1 triple knockout mouse model. However, whether FOXA2 is an essential driver of NEPC, and the underlying mechanism in shaping epigenetic landscape of NEPC is largely unknown.
Project description:Following extensive treatment with androgen receptor (AR) pathway inhibitors, a significant number of metastatic prostate cancer develop treatment resistance, and approximately 20% of these castration-resistant prostate cancers (CRPC) transdifferentiate, at least partially, into neuroendocrine (NE) prostate cancer (NEPC).In human cancer, FOXA2 is highly expressed in most of NEPC and a small portion of CRPC patients, has been suggested as a marker of NEPC and elevated in other NE lineage cancers including SCLC. In addition, preclinical studies demonstrated that Foxa2 is required for NEPC tumor growth and metastasis in TRAMP mouse model and associated with NEPC transformation in Pten, Trp53, and Rb1 triple knockout mouse model. However, whether FOXA2 is an essential driver of NEPC, and the underlying mechanism in shaping epigenetic landscape of NEPC is largely unknown.