Long Noncoding RNA 00472: A Novel Biomarker in Human Diseases

Long non-coding RNAs (lncRNAs) play important roles in human diseases. They control gene expression levels and influence various biological processes through multiple mechanisms. Functional abnormalities in lncRNAs are strongly associated with occurrence and development of various diseases. LINC00472, which is located on chromosome 6q13, is involved in several human diseases, particularly cancers of the breast, lung, liver, osteosarcoma, bladder, colorectal, ovarian, pancreatic and stomach. Importantly, LINC00472 can be used as a biomarker for breast cancer cell sensitivity to chemotherapeutic regimens, including doxorubicin. LINC00472 is regulated by microRNAs and several signaling pathways. However, the significance of LINC00472 in human diseases has not been clearly established. In this review, we elucidate on the significance of LINC00472 in various human diseases, indicating that LINC00472 may be a diagnostic, prognostic as well as therapeutic target for these diseases.

Implementation of a novel optogenetic tool in mammalian cells based on a split T7 RNA polymerase

Optogenetic tools are widely used to control gene expression dynamics both in prokaryotic and eukaryotic cells. These tools are used in a variety of biological applications from stem cell differentiation to metabolic engineering. Despite some tools already available in bacteria, no light-inducible system currently exists to orthogonally control gene expression in mammalian cells. Such a tool would be particularly important in synthetic biology, where orthogonality is advantageous to achieve robust activation of synthetic networks. Here we implement, characterize and optimize a new orthogonal optogenetic tool in mammalian cells based on a previously published system in bacteria called Opto-T7RNAPs. The tool consists of a split T7 RNA polymerase coupled with the blue light-inducible magnets system (mammalian OptoT7, mOptoT7). In our study we exploited the T7 polymerase's viral origins to tune our system's expression level, reaching up to 20-fold change activation over the dark control. mOptoT7 is used here to generate mRNA for protein expression, shRNA for protein inhibition and Pepper aptamer for RNA visualization. Moreover, we show that mOptoT7 can mitigate gene expression burden when compared to other optogenetic constructs. These properties make mOptoT7 a new powerful tool to use when orthogonality and viral-like RNA species are desired in both synthetic biology and basic science applications.

Transcriptional Regulation of the Colorectal Cancer Stem Cell Markers, Nanog and Oct4, Induced by a Thermodynamic-Based Therapy Approach

Background: Cancer stem cells (CSC) play a crucial role in tumorigenesis, recurrence, metastasis, and chemoresistanc. Some studies suggest that hyperthermia and photodynamic therapy (PDT) may be effective for cancer treatment, particularly when combined with other therapeutic approaches. However, the results are conflicting. Our aim was to evaluate the effect of hyperthermia combined with PDT on colorectal CSC viability and the gene expression of the CSC markers.Results: Cell viability decrased by PDT (P=0.015) and the combination therapy (P=0.006) but not hyperthermia alone (P=0.4) compared to control. Gene expression of CSC markers significantly decreased in all therapies. Conclusion: Hyperthermia combined with PDT was more efficient in eliminating tumors than hyperthermia or PDT alone.

Src acts with WNT/FGFRL signaling to pattern the planarian anteroposterior axis

Tissue identity determination is critical for regeneration, and the planarian anteroposterior (AP) axis uses positional control genes expressed from bodywall muscle to determine body regionalization. Canonical Wnt signaling establishes anterior versus posterior pole identities through notum and wnt1 signaling, and two Wnt/FGFRL signaling pathways control head and trunk domains, but their downstream signaling mechanisms are not fully understood. Here we identify a planarian Src homolog that restricts head and trunk identities to anterior positions. src-1(RNAi) animals formed enlarged brains and ectopic eyes and also duplicated trunk tissue, similar to a combination of Wnt/FGFRL RNAi phenotypes. src-1 was required for establishing territories of positional control gene expression, indicating it acts at an upstream step in patterning the AP axis. Double RNAi experiments and eye regeneration assays suggest src-1 can act in parallel to at least some Wnt and FGFRL factors. Co-inhibition of src-1 with other posterior-promoting factors led to dramatic patterning changes and a reprogramming of Wnt/FGFRLs into controlling new positional outputs. These results identify src-1 as a factor that promotes robustness of the AP positional system that instructs appropriate regeneration.

microRNA Utilize as a Potential Tool for Stress Tolerance in Plants

This chapter describe the possibilities of MicroRNAs (miRNAs) in crop plants gene expression regulation in different metabolic pathways. Several current researches have shown different environmental stresses induce abnormal expression of miRNA, thus signifying that miRNAs may be an appropriate tool for genetical improvement in plant for stress tolerance. These miRNAs mainly control gene expression through translational inhibition. Generally, stress induce miRNAs-based inhibition of their target mRNAs, however, positive transcription factors accumulated and become more active after mRNA inhibition. Initially, researchers were mainly focused on miRNA identification, appropriate to specific or multiple environmental condition, expression profiling and recognize their roles in stress tolerance. Transformed miRNA expression studied in some plant species for better understanding of plant development and stress tolerance such as heavy metal, salinity, temperature, drought and nutrient deficiency. All these findings indicate that miRNAs act as a potential tool for genetic engineering and to enhance stress tolerance in crop plants.

miRNA can be a part of both the onset and cure of Coronary heart disease.

Cardiovascular disease causes the worst destruction. The study suggests that miRNAs are involved in the cause, occurrence, and prognosis of CVD. Even though they were discovered in 1993, their functions have not been well understood; more recently, they are known to control gene expression as well as well as fine-tune many biochemical processes. A myriad of miRNAs contribute to the pathogenesis of coronary diseases. Most experiments on miRN have shown that miRNA is either increased or decreased under various pathophysiological conditions, but its function in CVD remains a mystery. often suggested to be involved in the pathophysiology of CVD The discovery of disease biomarkers that are useful in the processing would highlight the relevance of miRNAs for diagnostics and therapy development of CVDs. During the early stages, the use of miRNAs as therapies has the potential to impact therapeutics. More refined technologies are also required to develop miRNA as biomarkers and treatments Indeed, additional regional and/population research is needed to address any possible challenges or issues. The introduction of new gene therapies discoveries is on the way.

An intein-split transactivator for intersectional neural imaging and optogenetic manipulation

The complexity of brain circuitry is manifested by numerous cell types based on genetic marker, location and neural connectivity. Cell-type specific recording and manipulation is essential to disentangle causal neural mechanisms in physiology and behavior; however, many current approaches are largely limited by number of intersectional features, incompatibility of common effectors and insufficient gene expression. To tackle these limitations, we devise an intein-based intersectional synthesis of transactivator (IBIST) to selectively control gene expression of common effectors in specific cell types defined by a combination of multiple features. We validate the specificity and sufficiency of IBIST to control common effectors including fluorophores, optogenetic opsins and Ca2+ indicators in various intersectional conditions in vivo. Using IBIST-based Ca2+ imaging, we show that the IBIST can intersect up to five features, and that hippocampal cells tune differently to distinct emotional valences depending on the pattern of projection targets. Collectively, the IBIST multiplexes the capability to intersect cell-type features and is compatible with common effectors to effectively control gene expression, monitor and manipulate neural activities.

A unified mechanism for the control of Drosophila wing growth by the morphogens Decapentaplegic and Wingless

Development of the Drosophila wing—a paradigm of organ development—is governed by 2 morphogens, Decapentaplegic (Dpp, a BMP) and Wingless (Wg, a Wnt). Both proteins are produced by defined subpopulations of cells and spread outwards, forming gradients that control gene expression and cell pattern as a function of concentration. They also control growth, but how is unknown. Most studies have focused on Dpp and yielded disparate models in which cells throughout the wing grow at similar rates in response to the grade or temporal change in Dpp concentration or to the different amounts of Dpp “equalized” by molecular or mechanical feedbacks. In contrast, a model for Wg posits that growth is governed by a progressive expansion in morphogen range, via a mechanism in which a minimum threshold of Wg sustains the growth of cells within the wing and recruits surrounding “pre-wing” cells to grow and enter the wing. This mechanism depends on the capacity of Wg to fuel the autoregulation of vestigial (vg)—the selector gene that specifies the wing state—both to sustain vg expression in wing cells and by a feed-forward (FF) circuit of Fat (Ft)/Dachsous (Ds) protocadherin signaling to induce vg expression in neighboring pre-wing cells. Here, we have subjected Dpp to the same experimental tests used to elucidate the Wg model and find that it behaves indistinguishably. Hence, we posit that both morphogens act together, via a common mechanism, to control wing growth as a function of morphogen range.

Cell type–specific microRNA therapies for myocardial infarction

Current interventions fail to recover injured myocardium after infarction and prompt the need for development of cardioprotective strategies. Of increasing interest is the therapeutic use of microRNAs to control gene expression through specific targeting of mRNAs. In this Review, we discuss current microRNA-based therapeutic strategies, describing the outcomes and limitations of key microRNAs with a focus on target cell types and molecular pathways. Last, we offer a perspective on the outlook of microRNA therapies for myocardial infarction, highlighting the outstanding challenges and emerging strategies.