Long Non-coding RNA Double Homeobox A Pseudogene 8: A Novel Oncogenic Propellant in Human Cancer

A growing number of studies are reporting important roles played by long non-coding RNAs (lncRNAs) in various pathological and physiological processes. LncRNAs are implicated in numerous genomic regulatory functions at different levels, including regulation of transcription, post-transcriptional processes, genomic stability, and epigenetic genome modifications. Double homeobox A pseudogene 8 (DUXAP8), a novel lncRNA, has been reported to be involved in many cancers, including gastric, colorectal, esophageal, bladder, oral, ovarian, lung, and pancreatic cancers as well as hepatocellular carcinoma (HCC). DUXAP8 plays specific oncogenic roles via numerous malignancies promoting pathways. DUXAP8 is frequently dysregulated in multiple cancers, acting as a sponge to downregulate various tumor-suppressing microRNA activities. In this review, we comprehensively explore DUXAP8 expression and prognosis across cancer types, and systematically summarize current evidence concerning the functions and molecular mechanisms of DUXAP8 in tumorigenesis and progression. We conclude that DUXAP8 is a potential biomarker and therapeutic target for multiple cancers.

Genome Editing for the Development of Rice Resistance against Stresses: A Review

Food security is the most crucial issue faced by humans considering the rising population. Rice, a staple food consumed by nearly 50% of the world’s population, faces challenges to meet the consumers’ demand to ensure self-sufficiency amidst various abiotic and biotic stresses. Drought, salinity, heat, and infection by bacteria and viruses are the main challenges in rice cultivation. Genome editing technology provides abundant opportunities to implement selective genome modifications. Moreover, it finds the functional implications of different genome components in rice and provides a new approach for creating rice varieties tolerant of stresses. This review focuses on rice production worldwide and challenges faced in rice cultivation, and current genome editing tools available that can be utilised for crop breeding and improvement. In addition, the application of genome editing to develop biotic and abiotic resistance rice varieties is critically discussed.

Extracellular and Intracellular Factors in Brain Cancer

The external and internal factors of the cell are critical to glioma initiation. Several factors and molecules have been reported to be implicated in the initiation and progression of brain cancer. However, the exact sequence of events responsible for glioma initiation is still unknown. Existing reports indicate that glioma stem cells are the cell of glioma origin. During cell division, chromosome breakage, DNA alteration increases the chance of cell genome modifications and oncogene overexpression. Although there is a high risk of gene alteration and oncogene overexpression, not everyone develops cancer. During embryogenesis, the same oncogenes that promote cancers have also been reported to be highly expressed, but this high expression which does not lead to carcinogenesis raises questions about the role of oncogenes in carcinogenesis. The resistance of cancer cells to drugs, apoptosis, and immune cells does not rely solely on oncogene overexpression but also on the defect in cell organelle machinery (mitochondria, endoplasmic reticulum, and cytoskeleton). This review discusses factors contributing to cancer; we report the dysfunction of the cell organelles and their contribution to carcinogenesis, while oncogene overexpression promotes tumorigenesis, maintenance, and progression through cell adhesion. All these factors together represent a fundamental requirement for cancer and its development.

Genetic Technologies for Sustainable Management of Insect Pests and Disease Vectors

Recent advancements in genetic and genome editing research, augmented by the discovery of new molecular tools such as CRISPR, have revolutionised the field of genetic engineering by enabling precise site-specific genome modifications with unprecedented ease. These technologies have found a vast range of applications, including the development of novel methods for the control of vector and pest insects. According to their genetic makeup and engineering, these tools can be tuned to impose different grades of impact on the targeted populations. Here, we review some of the most recent genetic control innovations under development, describing their molecular mechanisms and performance, highlighting the sustainability potentials of such interventions.

Chromosome and Molecular Analyses Reveal Significant Karyotype Diversity and Provide New Evidence on the Origin of Aegilops columnaris

Aegilops columnaris Zhuk. is tetraploid grass species (2n = 4x = 28, UcUcXcXc) closely related to Ae. neglecta and growing in Western Asia and a western part of the Fertile Crescent. Genetic diversity of Ae. columnaris was assessed using C-banding, FISH, nuclear and chloroplast (cp) DNA analyses, and gliadin electrophoresis. Cytogenetically Ae. columnaris was subdivided into two groups, C-I and C-II, showing different karyotype structure, C-banding, and FISH patterns. C-I group was more similar to Ae. neglecta. All types of markers revealed significant heterogeneity in C-II group, although group C-I was also polymorphic. Two chromosomal groups were consistent with plastogroups identified in a current study based on sequencing of three chloroplast intergenic spacer regions. The similarity of group C-I of Ae. columnaris with Ae. neglecta and their distinctness from C-II indicate that divergence of the C-I group was associated with minor genome modifications. Group C-II could emerge from C-I relatively recently, probably due to introgression from another Aegilops species followed by a reorganization of the parental genomes. Most C-II accessions were collected from a very narrow geographic region, and they might originate from a common ancestor. We suggest that the C-II group is at the initial stage of species divergence and undergoing an extensive speciation process.

Cas9-mediated genome editing in Giardia intestinalis

CRISPR/Cas9 system is an extremely powerful technique that is extensively used for different genome modifications in various organisms including parasitic protists. Giardia intestinalis, a protozoan parasite infecting large number of people around the world each year, has been eluding the use of CRISPR/Cas9 technique so far which may be caused by its rather complicated genome containing four copies of each gene in its two nuclei. Apart from only single exception (Ebneter et al., 2016), without the use of CRISPR/Cas9 technology in its full potential, researchers in the field have not been able to establish knock-out cell lines to study the functional aspect of Giardia genes. In this work, we show the ability of in-vitro developed CRISPR/Cas9 components to successfully edit the genome of G. intestinalis. Moreover, we used self-propagating CRISPR/Cas9 system to establish full knock out cell lines for mem, cwp1 and mlf1 genes. We also show that the system function even for essential genes, as we knocked-down tom40, lowering the amount of Tom40 protein by more than 90%. Further, we tested the length of homologous arms needed for successful integration of homology recombination cassette used for genome editing. Taken together, our work introduces CRISPR/Cas9 to Giardia for routine use in the lab, further extending the catalogue of molecular tolls available for genetic manipulation of the protist and allowing researchers to study the function of Giardia genes properly for the first time.

Genome Modifications Involved in Developmental Programs of the Placental Trophoblast

The placental trophoblast cells give an example of profound genome modifications that lead to whole-genome multiplication, aneuploidy, under-replication of some genes or their clusters as well as, by contrast, gene amplification. These events are included into program of differentiation of functionally different cell lineages. In some cases the trophoblast cell differentiation involves depolyploidization achieved by non-mitotic division. Aneuploidy may be also accounted for by the unusual mitoses characteristic of Invertebrates and plants; in mammalian it may result from hypomethylation of centromere chromosome regions. The giant (endopolyploid) trophoblast cells organization includes “loose nucleosomes” accounted for by the non-canonical histone variants, i.e. H2AX, H2AZ, and H3. 3 . In the human extravillous trophoblast cells that, like murine TGC, invade endometrium, there occured significant changes of methylation as compared to non-invasive trophoblast cell populations . Meantime, some genes show hypermethylation connected with start of trophoblast lineages specification. Thus, despite the limited possibilities of chromosome visualization trophoblast cells represent an interesting model to investigate the role of modification of gene copy number and their expression that is important for the normal or abnormal cell differentiation.

CRISPR/Cas9-mediated genome editing in Brassica

CRISPR/Cas9 is a valuable tool for both basic and applied research that has been widely applied to different plant species. In this chapter, we reviewed the application of CRISPR/Cas9 genome editing toolkit in Brassica crops. We also provided a case study in Brassica napus. Collectively, our results demonstrate that CRISPR/Cas9 is an efficient tool for creating targeted genome modifications at multiple loci in B. napus. These findings open many doors for biotechnological applications in oilseed crops.

Chromosome and Molecular Analyses Reveal Significant Intraspecific Karyotype Diversity and Provide New Evidence on the Origin of Tetraploid Grass Aegilops columnaris

Aegilops columnaris Zhuk. is tetraploid grass species (2n=4x=28, UcUcXcXc) closely related to Ae. neglecta and growing in Western Asia and a western part of the Fertile Crescent. Genetic diversity of Ae. columnaris was assessed using C-banding, FISH, nuclear and chloroplast (cp)DNA analyses, and gliadin electrophoresis. Cytogenetically Ae. columnaris was subdivided into two groups, C-I and C-II, showing different karyotype structure, C-banding and FISH patterns. Group C-I was more similar to Ae. neglecta. All types of markers revealed significant heterogeneity of the C-II group, although group C-I was also polymorphic. Two chromosomal groups were consistent with plastogroups identified in a current study based on sequencing of three chloroplast intergenic spacer regions. The similarity of group C-I of Ae. columnaris with Ae. neglecta and their distinctness from C-II indicate that divergence of the C-I group was associated with minor genome modifications. Group C-II could emerge from C-I relatively recently, probably due to introgression from another Aegilops species followed by a reorganization of the parental genomes. Most C-II accessions were collected from the very narrow geographic region, and they might originate from a common ancestor. We suggest that the C-II group is at the initial stage of species divergence and undergoing an extensive speciation process.

The NIH Somatic Cell Genome Editing program

The move from reading to writing the human genome offers new opportunities to improve human health. The United States National Institutes of Health (NIH) Somatic Cell Genome Editing (SCGE) Consortium aims to accelerate the development of safer and more-effective methods to edit the genomes of disease-relevant somatic cells in patients, even in tissues that are difficult to reach. Here we discuss the consortium’s plans to develop and benchmark approaches to induce and measure genome modifications, and to define downstream functional consequences of genome editing within human cells. Central to this effort is a rigorous and innovative approach that requires validation of the technology through third-party testing in small and large animals. New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled—along with validated datasets—into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit—and the knowledge generated by its applications—as a means to accelerate the clinical development of new therapies for a wide range of conditions.