Copy number variations are progressively associated with the pathogenesis of colorectal cancer in ulcerative colitis

AIM: To evaluate the association of known copy number variations(CNVs) in ulcerative colitis(UC) progressing to colorectal cancer.METHODS: Microsatellite instability analysis using the National Cancer Institute's panel of markers, and CNV association studies using Agilent 2 × 105 k arrays were done in tissue samples from four patient groups with UC: those at low risk(LR) or high risk of developing colorectal cancer, those with premalignant dysplastic lesions, and those with colitis-associated colorectal cancer(CAC). DNA from tissue samples of these groups were independently hybridized on arrays and analyzed. The data obtained were further subjected to downstream bioinformatics enrichment analysis to examine the correlation with CAC progression.RESULTS: Microarray analysis highlighted a progressive increase in the total number of CNVs [LR(n = 178) vs CAC(n = 958), 5.3-fold], gains and losses [LR(n = 37 and 141) vs CAC(n = 495 and 463), 13.4- and 3.3-fold, respectively], size [LR(964.2 kb) vs CAC(10540 kb), 10.9-fold] and the number of genes in such regions [LR(n = 119) vs CAC(n = 455), 3.8-fold]. Chromosomewise analysis of CNVs also showed an increase in the number of CNVs across each chromosome. There were 38 genes common to all four groups in the study; 13 of these were common to cancer genes from the Genetic Disease Association dataset. The gene set enrichment analysis and ontology analysis highlighted many cancerassociated genes. All the samples in the different groupswere microsatellite stable.CONCLUSION: Increasing numbers of CNVs are associated with the progression of UC to CAC, and warrant further detailed exploration.

Epigenetics mechanisms and degenerative diseases

Epigenetic regulations are heritable changes in gene expression that occur in the absence of alterations in DNA sequences. Various epigenetic mechanisms include histone modifications and DNA methylations. In this review, we examine methods to study DNA methylations and their contribution to degenerative diseases by mediating the complex gene-by-environment interactions. Such epigenetic modifications despite being heritable and stably maintained are also potentially reversible and there is scope for the development of epigenetic therapies for this disease.

Role of gap junctions between keratinocyte and melanocyte in melanogenesis

The process ofmelanogenesis in melanocytes and the transport of melanin in the form ofmelanosomes to the neighboring keratinocytes are the key steps in human skin pigmentation. Keratinocytes and melanocytes interact in intricate manner to maintain the homeostasis. The present study was designed to understand the role of cell-cell interaction through the gap junctions between melanocytes and keratinocytes on melanogenesis. We show that, inhibition of the gap junctional activity between human keratinocytes and melanocytes in a coculture system using gap junction blocker lowers the expression of key regulatory genes of melanogenesis such as tyrosinase and microphthalmia- associated transcription factor （MITF）. This was followed by concurrent decrease in tyrosinase protein levels and activity. Our results show the preliminary evidence for the regulation of melanogenesis in melanocytes through direct gap junctional communication by keratinocytes. Deciphering the mechanism and factors involved in the process would uncover the significance of gap junctions in melanogenesis.

Cell size: a key determinant of meristematic potential in plant protoplasts

Metabolic pathway reconstruction and gene edits for native natural product synthesis in single plant cells are considered to be less complicated when compared to the production of non-native metabolites.Being an efficient eukaryotic system,plants encompass suitable post-translational modifications.However,slow cell division rate and heterogeneous nature is an impediment for consistent product retrieval from plant cells.Plant cell synchrony can be attained in cultures developed in vitro.Isolated plant protoplasts capable of division,can potentially enhance the unimpaired yield of target bioactives,similar to microbes and unicellular eukaryotes.Evidence from yeast experiments suggests that‘critical cell size’and division rates for enhancement machinery,primarily depend on culture conditions and nutrient availability.The cell size control mechanisms in Arabidopsis shoot apical meristem is analogous to yeast notably,fission yeast.If protoplasts isolated from plants are subjected to cell size studies and cell cycle progression in culture,it will answer the underlying molecular mechanisms such as,unicellular to multicellular transition states,longevity,senescence,‘cell-size resetting’during organogenesis,and adaptation to external cues.