Alex J Smith

Bio: Alex J Smith is an academic researcher from University of Colorado Boulder. The author has contributed to research in topics: Frizzled & Wnt signaling pathway. The author has an hindex of 1, co-authored 1 publications receiving 1 citations.

Non-Coding RNA and Frizzled Receptors in Cancer

Abstract: Frizzled receptors have been long recognized for their role in Wnt/β-catenin signaling, a pathway known for its tumorigenic effects. More recent studies of frizzled receptors include efforts to understand non-coding RNA (ncRNA) regulation of these receptors in cancer. It has become increasingly clear that ncRNA molecules are important for regulating the expression of both oncogenic and tumor-suppressive proteins. The three most commonly described ncRNA molecules are microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Here, we review ncRNA molecules that directly or indirectly affect frizzled protein expression and downstream signaling. Exploring these interactions highlights the potential of incorporating ncRNA molecules into cancer prevention and therapy strategies that target frizzled receptors. Previous investigations of frizzled receptors and ncRNA have established strong promise for a role in cancer progression, but additional studies are needed to provide the substantial pre-clinical evidence required to translate findings to clinical applications.

miRNAs as cornerstones in chronic lymphocytic leukemia pathogenesis and therapeutic resistance- An emphasis on the interaction of signaling pathways.

Abstract: Chronic lymphocytic leukemia (CLL) accounts for the vast majority of cases of leukemia. Patients of advanced age are more likely to develop the condition, which has a highly varied clinical course. Consideration of illness features and preceding treatment sequence, as well as patient preferences and comorbidities, is necessary for selecting the appropriate treatment for the appropriate patient. Therefore, there is an urgent need for novel biomarkers with high sensitivity and specificity to detect CLL early, monitor CLL patients, select the treatment responders, and reduce ineffective treatment, unwanted side effects, and unnecessary expenses. In both homeostasis and illness, microRNAs (miRNAs/miRs) play a vital role as master regulators of gene expression and, by extension, protein expression. MiRNAs typically reduce the stability of mRNAs, including those encoding genes involved in tumorigenesis processes as cell cycle regulation, inflammation, stress response, angiogenesis, differentiation, apoptosis, and invasion. Due to their unique properties, miRNAs are rapidly being exploited as accurate biomarkers for illness detection, and medicines based on miRNA targets are finding widespread application in clinical practice. Accordingly, the current review serves as a quick primer on CLL and the biogenesis of miRNAs. In addition to providing a brief overview of the miRNAs whose function in the progression of CLL has been established by recent in vitro or in vivo research through articulating the influence of these miRNAs on a wide variety of cellular functions, including increased proliferative potential; support for angiogenesis; cell cycle aberration; evasion of apoptosis; promotion of metastasis; and reduced sensitivity to specific treatments.

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance.

Abstract: Hormone therapy is one of the most effective breast cancer treatments, however, its application is limited by the progression of hormonal resistance, both primary or acquired. The development of hormonal resistance is caused either by an irreversible block of hormonal signalling (suppression of the activity or synthesis of hormone receptors), or by activation of oestrogen-independent signalling pathways. Recently the effect of exosome-mediated intercellular transfer of hormonal resistance was revealed, however, the molecular mechanism of this effect is still unknown. Here, the role of exosomal miRNAs (microRNAs) in the transferring of hormonal resistance in breast cancer cells has been studied. The methods used in the work include extraction, purification and RNAseq of miRNAs, transfection of miRNA mimetics, immunoblotting, reporter analysis and the MTT test. Using MCF7 breast cancer cells and MCF7/T tamoxifen-resistant sub-line, we have found that some miRNAs, suppressors of oestrogen receptor signalling, are overexpressed in the exosomes of the resistant breast cancer cells. The multiple (but not single) transfection of one of the identified miRNA, miR-181a-2, into oestrogen-dependent MCF7 cells induced the irreversible tamoxifen resistance associated with the continuous block of the oestrogen receptor signalling and the activation of PI3K/Akt pathway. We suppose that the miRNAs-ERα suppressors may act as trigger agents inducing the block of oestrogen receptor signalling and breast cancer cell transition to an aggressive oestrogen-independent state.

Circular RNAs modulate Hippo-YAP signaling: functional mechanisms in cancer

Abstract: The Hippo signaling pathway is an evolutionarily conserved network that regulates organ size and tissue homeostasis in mammals. This pathway controls various cell functions, such as growth, proliferation, survival, apoptosis, and stemness by switching 'on' or 'off' its inhibitory and/or transcriptional module, thereby regulating target gene(s) expression. Altered Hippo signaling has been implicated in various forms of cancers. Increasing evidence suggests cross-talk between the Hippo signaling pathway and non-coding RNAs, in particular circular RNAs (circRNAs). In this context, the current review presents the mechanistic interplay between the Hippo pathway and related circRNAs in various forms of cancers, along with the capabilities of these circRNAs to function either as tumor suppressors or oncogenes through miRNA sponging or protein binding mechanisms. Furthermore, we discuss the constraints and limitations in circRNA mechanistic studies while highlighting some outstanding questions regarding the roles of circRNAs associated with the Hippo-YAP pathway in cancer. Finally, we delineate the potential of these circRNAs to be employed as diagnostic and prognostic biomarkers, as well as molecular hotspots for cancer therapy.

The Emerging Role of Extracellular Vesicle Derived From Neurons/Neurogliocytes in Central Nervous System Diseases: Novel Insights Into Ischemic Stroke

Abstract: Neurons and neurogliocytes (oligodendrocytes, astrocytes, and microglia) are essential for maintaining homeostasis of the microenvironment in the central nervous system (CNS). These cells have been shown to support cell-cell communication via multiple mechanisms, most recently by the release of extracellular vesicles (EVs). Since EVs carry a variety of cargoes of nucleic acids, lipids, and proteins and mediate intercellular communication, they have been the hotspot of diagnosis and treatment. The mechanisms underlying CNS disorders include angiogenesis, autophagy, apoptosis, cell death, and inflammation, and cell-EVs have been revealed to be involved in these pathological processes. Ischemic stroke is one of the most common causes of death and disability worldwide. It results in serious neurological and physical dysfunction and even leads to heavy economic and social burdens. Although a large number of researchers have reported that EVs derived from these cells play a vital role in regulating multiple pathological mechanisms in ischemic stroke, the specific interactional relationships and mechanisms between specific cell-EVs and stroke treatment have not been clearly described. This review aims to summarize the therapeutic effects and mechanisms of action of specific cell-EVs on ischemia. Additionally, this study emphasizes that these EVs are involved in stroke treatment by inhibiting and activating various signaling pathways such as ncRNAs, TGF-β1, and NF-κB.