The date palm is one of the oldest cultivated fruit trees. It is critical in many ways to cultures in arid lands by providing highly nutritious fruit while surviving extreme heat and environmental conditions. Despite its importance from antiquity, few genetic resources are available for improving the productivity and development of the dioecious date palm. To date there has been no genetic map and no sex chromosome has been identified.

Circular RNAs (circRNAs) that form through non-canonical backsplicing events of pre-mRNA transcripts are evolutionarily conserved and abundantly expressed across species. However, the functional relevance of circRNAs remains a topic of debate. We identified one of the highly expressed circRNA (circANKRD12) in cancer cell lines and characterized it validated it by Sanger sequencing, Real-Time PCR. siRNA mediated silencing of the circular junction of circANKRD12 was followed by RNA Seq analysis of circANKRD12 silenced cells and control cells to identify the differentially regulated genes. A series of cell biology and molecular biology techniques (MTS assay, Migration analysis, 3D organotypic models, Real-Time PCR, Cell cycle analysis, Western blot analysis, and Seahorse Oxygen Consumption Rate analysis) were performed to elucidate the function, and underlying mechanisms involved in circANKRD12 silenced breast and ovarian cancer cells. In this study, we identified and characterized a circular RNA derived from Exon 2 and Exon 8 of the ANKRD12 gene, termed here as circANKRD12. We show that this circRNA is abundantly expressed in breast and ovarian cancers. The circANKRD12 is RNase R resistant and predominantly localized in the cytoplasm in contrast to its source mRNA. We confirmed the expression of this circRNA across a variety of cancer cell lines and provided evidence for its functional relevance through downstream regulation of several tumor invasion genes. Silencing of circANKRD12 induces a strong phenotypic change by significantly regulating cell cycle, increasing invasion and migration and altering the metabolism in cancer cells. These results reveal the functional significance of circANKRD12 and provide evidence of a regulatory role for this circRNA in cancer progression. Our study demonstrates the functional relevance of circANKRD12 in various cancer cell types and, based on its expression pattern, has the potential to become a new clinical biomarker.

The date palm is one of the oldest cultivated fruit trees. The tree can withstand high temperatures and low water and the fruit can be stored dry offering nutrition across the year. The first region of cultivation is believed to be near modern day Iraq, however, where and if the date palm was domesticated is still a topic of debate. Recent studies of chloroplast and genomic DNA revealed two major subpopulations of cultivars centered in both the Eastern range of date palm cultivation including Arabian Peninsula, Iraq and parts of South Asia, and the Western range, including North Africa. To better understand the origins of date palm cultivation we sequenced and analyzed over 200 mitochondrial and chloroplast genomes from a geographically diverse set of date palms. Here we show that, based on mitochondrial and chloroplast genome-wide genotyping data, the most common cultivated date palms contain 4 haplotypes that appear associated with geographical region of cultivar origin. These data suggest at least 3 and possibly 4 original maternal contributions to the current date palm population and doubles the original number. One new haplotype was found mainly in Tunisia, Algeria and Egypt and the second in Iraq, Iran and Oman. We propose that earliest date palm cultivation occurred independently in at least 3 distinct locations. This discovery will further inform understanding of the history and origins of cultivated date palm.

Transcriptome profiling of 3D models compared to 2D models in various cancer cell lines shows differential expression of TGF-β-mediated and cell adhesion pathways. Presence of TGF-β in these cell lines shows an increased invasion potential which is specific to cell type. In the present study, we identified exogenous addition of TGF-β can induce Epithelial to Mesenchymal Transition (EMT) in a few cancer cell lines. RNA sequencing and real time PCR were carried out in different ovarian cancer cell lines to identify molecular profiling and metabolic profiling. Since EMT induction by TGF-β is cell-type specific, we decided to select two promising ovarian cancer cell lines as model systems to study EMT. TGF-β modulation in EMT and cancer invasion were successfully depicted in both 2D and 3D models of SKOV3 and CAOV3 cell lines. Functional evaluation in 3D and 2D models demonstrates that the addition of the exogenous TGF-β can induce EMT and invasion in cancer cells by turning them into aggressive phenotypes. TGF-β receptor kinase I inhibitor (LY364947) can revert the TGF-β effect in these cells. In a nutshell, TGF-β can induce EMT and migration, increase aggressiveness, increase cell survival, alter cell characteristics, remodel the Extracellular Matrix (ECM) and increase cell metabolism favorable for tumor invasion and metastasis. We concluded that transcriptomic and phenotypic effect of TGF-β and its inhibitor is cell-type specific and not cancer specific.

Circular RNAs were once considered artifacts of transcriptome sequencing but have recently been identified as functionally relevant in multiple cancers. Although there is still no clear main function of circRNAs, several studies have revealed that circRNAs are expressed in a variety of eukaryotic organisms, demonstrate conservation across species, and are expressed in a regulated manner often independent of their parental linear isoforms. circNFATC3, an abundant and uncharacterized circular isoform of NFATC3 gene (which is formed form backsplicing of exon 2 and 3) in solid tumors was identified from transcriptomic data. Here we show that circNFATC3 gain of and loss of function experiments using RNAi mediated circRNA silencing and circular mini vector-mediated overexpression of circularized constructs in breast and ovarian cancer cell lines affects molecular phenotypes. Knockdown of circNFATC3 induces a reduction in cell proliferation, invasion, migration, and oxidative phosphorylation. Gain of function of circNFATc3 in MDA-MB -231 cells and SKOV3 cells shows a significant increase in cell proliferation, migration, and respiration. The above results suggest that circNFATC3 is a functionally relevant circular RNA in cancer