A multi-omics analysis of bone morphogenetic protein 5 (BMP5) mRNA expression and clinical prognostic outcomes in different cancers using bioinformatics approaches

Cumulative studies have provided controversial evidence for the prognostic values of bone morphogenetic protein 5 (BMP5) in different types of cancers such as colon, breast, lung, bladder, and ovarian cancer. To address the inconsistent correlation of BMP5 expression with patient survival and molecular function of BMP5 in relation to cancer progression, we performed a systematic study to determine whether BMP5 could be used as a prognostic marker in human cancers. BMP5 expression and prognostic values were assessed using different bioinformatics tools such as ONCOMINE, GENT, TCGA, GEPIA, UALCAN, PrognoScan, PROGgene V2 server, and Kaplan–Meier Plotter. In addition, we used cBioPortal database for the identification and analysis of BMP5 mutations, copy number alterations, altered expression, and protein–protein interaction (PPI). We found that BMP5 is frequently down-regulated in our queried cancer types. Use of prognostic analysis showed negative association of BMP5 down-regulation with four types of cancer except for ovarian cancer. The highest mutation was found in the R321*/Q amino acid of BMP5 corresponding to colorectal and breast cancer whereas the alteration frequency was higher in lung squamous carcinoma datasets (>4%). In PPI analysis, we found 31 protein partners of BMP5, among which 11 showed significant co-expression (p-value 1). Pathway analysis of differentially co-expressed genes with BMP5 in breast, lung, colon, bladder and ovarian cancers revealed the BMP5-correlated pathways. Collectively, this data-driven study demonstrates the correlation of BMP5 expression with patient survival and identifies the involvement of BMP5 pathways that may serve as targets of a novel biomarker for various types of cancers in human

A Novel Approach to Epigenomic Profiling of Transposable Elements

ChIP-seq reads are notoriously difficult to assign to individual transposon copies. In particular, little is known about the locus-specific regulation of evolutionarily young transposable elements, which have been implicated in genome stability, gene regulation and innate immunity in a variety of developmental and disease contexts. Understanding of how individual copies are transcriptionally regulated cannot be appreciated without this information. To overcome this, I propose to leverage chromatin conformation information from Hi-ChIP data, a technique which combines Hi-C with ChIP-seq. As proximal (<50kb) chromatin interactions predominate, mappable genomic fragments are more likely to interact with repeats nearby than those lying far away. To implement this mapping strategy, we have developed PAtChER (Proximity-based alignment of Hi-ChIP ends to repeats). PAtChER employs information from Hi-ChIP chimeric reads to assign the multi-mapping read to a single location in the genome with high accuracy. Importantly, I demonstrate that PAtChER yields accurate protein enrichment profiles at individual repetitive loci. I then applied this to discover previously unappreciated protein positional information at individual transposable elements. This strategy will enable substantial improvements to our current understanding of transposon transcriptional regulation in health and disease and provide an invaluable tool to the transposon field

RNA, the Epicenter of Genetic Information

The origin story and emergence of molecular biology is muddled. The early triumphs in bacterial genetics and the complexity of animal and plant genomes complicate an intricate history. This book documents the many advances, as well as the prejudices and founder fallacies. It highlights the premature relegation of RNA to simply an intermediate between gene and protein, the underestimation of the amount of information required to program the development of multicellular organisms, and the dawning realization that RNA is the cornerstone of cell biology, development, brain function and probably evolution itself. Key personalities, their hubris as well as prescient predictions are richly illustrated with quotes, archival material, photographs, diagrams and references to bring the people, ideas and discoveries to life, from the conceptual cradles of molecular biology to the current revolution in the understanding of genetic information. Key Features Documents the confused early history of DNA, RNA and proteins - a transformative history of molecular biology like no other. Integrates the influences of biochemistry and genetics on the landscape of molecular biology. Chronicles the important discoveries, preconceptions and misconceptions that retarded or misdirected progress. Highlights major pioneers and contributors to molecular biology, with a focus on RNA and noncoding DNA. Summarizes the mounting evidence for the central roles of non-protein-coding RNA in cell and developmental biology. Provides a thought-provoking retrospective and forward-looking perspective for advanced students and professional researchers

DNA methylation changes associated with acquired platinum resistance in ovarian cancer

Despite high responses to initial chemotherapy most patients with ovarian cancer (OC) relapse and inevitably die from their disease. Aberrant DNA methylation is frequently seen in ovarian tumours and may provide biomarkers of clinical outcome or insight into mechanisms of chemoresistance. We firstly performed Differential Methylation Hybridisation (DMH) to identify loci that gained methylation between 34 matched cisplatin sensitive and resistant OC tumour cell lines. Differentially methylated loci identified were further validated by Methylation Specific PCR (MSP) and bisulphite pyrosequencing. Selected loci were further investigated for association with clinical outcome in primary OC tumour samples and matched tumour samples from patients' pre- and post-chemotherapy. Frequent increased methylation of a CpG island at the NR2E1 gene was identified in this experiment. Increased methylation correlated with decreased gene expression and could be reversed following treatment with a demethylating agent. Increased methylation at NR2E1 was observed between matched pre- and post-treatment tumour pairs. A novel biostatistical method, methylation linear discrimination analysis (MLDA), was next used to identify differentially methylated loci in sensitive and resistant A2780 human ovarian cell lines. Eight of nine loci identified were validated by MSP. A locus at the SP5 gene was further investigated by pyrosequencing and found to show a very high level methylation in most cell lines and ovarian tumours. Increased methylation correlated with decreased gene expression and this could be reversed using decitabine treatment. Knockdown of SP5 expression caused increased apoptosis. DMH was next used to identify loci that gained methylation between 3 in vivo derived matched sensitive and resistant cell lines. KIAA1383, a gene of unknown function, was identified and methylation shown to correlate with response to chemotherapy and progression-free survival (PFS) in patients with OC. Over-expression was found to attenuate the response to cisplatin, in the PEA2 cell line, as measured by cell cycle analysis

Oncogene and Cancer

This book describes a course of cancer growth starting from normal cells to cancerous form and the genomic instability, the cancer treatment as well as its prevention in form of the invention of a vaccine. Some diseases are also discussed in detail, such as breast cancer, leucaemia, cervical cancer, and glioma. Understanding cancer through its molecular mechanism is needed to reduce the cancer incidence. How to treat cancer more effectively and the problems like drug resistance and metastasis are very clearly illustrated in this publication as well as some research result that could be used to treat the cancer patients in the very near future. The book was divided into six main sections: 1. HER2 Carcinogenesis: Etiology, Treatment and Prevention; 2. DNA Repair Mechanism and Cancer; 3. New Approach to Cancer Mechanism; 4. New Role of Oncogenes and Tumor Suppressor Genes; 5. Non Coding RNA and Micro RNA in Tumorigenesis; 6. Oncogenes for Transcription Factor