Targeting circular RNAs as a therapeutic approach: current strategies and challenges

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: May 21, 2021

Abstract Significant progress has been made in circular RNA (circRNA) research recent years. Increasing evidence suggests that circRNAs play important roles many cellular processes, and their dysregulation is implicated the pathogenesis of various diseases. CircRNAs are highly stable usually expressed a tissue- or cell type-specific manner. Therefore, they currently being explored as potential therapeutic targets. Gain-of-function loss-of-function approaches typically performed using circRNA expression plasmids interference-based strategies, respectively. These strategies have limitations can be mitigated nanoparticle exosome delivery systems. Furthermore, developments show cre-lox system used to knockdown cell-specific While still early stages development, CRISPR/Cas13 shown promise knocking down with high specificity efficiency. In this review, we describe properties functions highlight significance disease. We summarize overexpress approach. Lastly, discuss major challenges propose future directions for development circRNA-based therapeutics.

Language: Английский

---

Oral squamous cell carcinomas: state of the field and emerging directions

International Journal of Oral Science, Journal Year: 2023, Volume and Issue: 15(1)

Published: Sept. 22, 2023

Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of oral cavity. It accounts for approximately 90% malignancies and impairs appearance, pronunciation, swallowing, flavor perception. In 2020, 377,713 OSCC cases were reported globally. According to Global Cancer Observatory (GCO), incidence will rise by 40% 2040, accompanied a growth in mortality. Persistent exposure various risk factors, including tobacco, alcohol, betel quid (BQ), human papillomavirus (HPV), lead development potentially malignant disorders (OPMDs), which are lesions with an increased developing into OSCC. Complex multifactorial, oncogenesis process involves genetic alteration, epigenetic modification, dysregulated tumor microenvironment. Although therapeutic interventions, such as chemotherapy, radiation, immunotherapy, nanomedicine, have been proposed prevent or treat OPMDs, understanding mechanism facilitate identification prognostic thereby improving efficacy treatment patients. This review summarizes mechanisms involved Moreover, current interventions methods OPMDs discussed comprehension provide several prospective outlooks fields.

Language: Английский

---

The interplay of ROS and the PI3K/Akt pathway in autophagy regulation

Biotechnology and Applied Biochemistry, Journal Year: 2021, Volume and Issue: 69(1), P. 248 - 264

Published: Jan. 15, 2021

Autophagy causes the breakdown of damaged proteins and organelles to their constituent components. The phosphatidylinositol 3-kinase (PI3K) pathway played an important role in regulating autophagic response cells changing reactive oxygen species (ROS) levels. PI3K α catalytic subunit inhibits autophagy, while its β promotes autophagy changes ROS downstream Akt protein acts against initiation increases levels under nutrient-rich conditions. by activating a mechanistic target rapamycin complex 1 (mTORC1) arresting gene expression. AMP-activated kinase (AMPK) counteracts actions. mTORC1 mTORC2 inhibit moderate levels, but high can promote cellular senescence via autophagy. Phosphatase tensin homolog (PTEN) are negative regulators pathway, it has proautophagic activities. Studies conducted on treated with flavonoids ionizing radiation showed that increase flavonoid-treated groups corresponded higher PTEN lowered leading occurrence In contrast, evoked caused lowering incidence

Language: Английский

---

IL-12 Family Cytokines in Cancer and Immunotherapy

Cancers, Journal Year: 2021, Volume and Issue: 13(2), P. 167 - 167

Published: Jan. 6, 2021

The IL-12 family cytokines are a group of unique heterodimeric that include IL-12, IL-23, IL-27, IL-35 and, most recently, IL-39. Recent studies have solidified the importance in shaping innate and adaptive immune responses cancer identified multipronged roles for distinct members, ranging from effector to regulatory functions. These could serve as promising candidates development immunomodulatory therapeutic approaches. Overall, can be considered an cytokine has been found engage anti-tumor immunity by activating Th1 response, which is required activation cytotoxic T NK cells tumor clearance. IL-23 IL-27 play dual immunity, they both activate promote growth favoring suppression. potent plays largely pro-tumorigenic role inhibiting cells. In this review, we summarize recent findings on control with emphasis primarily regulation. We underscore clinical implications use these either setting monotherapy or combination other conventional therapies more effective treatment malignancies.

Language: Английский

---

CTLA-4 in Regulatory T Cells for Cancer Immunotherapy

Cancers, Journal Year: 2021, Volume and Issue: 13(6), P. 1440 - 1440

Published: March 22, 2021

Immune checkpoint inhibitors (ICIs) have obtained durable responses in many cancers, making it possible to foresee their potential improving the health of cancer patients. However, immunotherapies are currently limited a minority patients and there is need develop better understanding basic molecular mechanisms functions pivotal immune regulatory molecules. cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) T (Treg) cells play roles hindering anticancer immunity. Treg suppress antigen-presenting (APCs) by depleting stimulating cytokines, producing immunosuppressive cytokines constitutively expressing CTLA-4. CTLA-4 molecules bind CD80 CD86 with higher affinity than CD28 act as competitive APCs. The purpose this review summarize state-of-the-art underlining regulation correlation ICI response expression from preclinical clinical studies for possibly CTLA-4-based immunotherapies, while highlighting knowledge gap.

Language: Английский

---

Ubiquitination-Proteasome System (UPS) and Autophagy Two Main Protein Degradation Machineries in Response to Cell Stress

Cells, Journal Year: 2022, Volume and Issue: 11(5), P. 851 - 851

Published: March 1, 2022

In response to environmental stimuli, cells make a series of adaptive changes combat the injury, repair damage, and increase tolerance stress. However, once damage is too serious repair, will undergo apoptosis protect overall through suicidal behavior. Upon external stimulation, some intracellular proteins turn into unfolded or misfolded protein, exposing their hydrophobic regions form protein aggregation, which may ultimately produce cells. Ubiquitin plays an important role in degradation these unnatural by tagging with ubiquitin chains ubiquitin-proteasome autophagy system. If two processes fail eliminate abnormal aggregates, move death. Dysregulation system (UPS) result development numerous diseases. This review focuses on molecular mechanisms UPS clearance relationship between dysregulation network

Language: Английский

---

Diversity and complexity of cell death: a historical review

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(8), P. 1573 - 1594

Published: Aug. 23, 2023

Abstract Death is the inevitable fate of all living organisms, whether at individual or cellular level. For a long time, cell death was believed to be an undesirable but unavoidable final outcome nonfunctioning cells, as inflammation inevitably triggered in response damage. However, experimental evidence accumulated over past few decades has revealed different types that are genetically programmed eliminate unnecessary severely damaged cells may damage surrounding tissues. Several death, including apoptosis, necrosis, autophagic and lysosomal which classified pyroptosis, necroptosis, NETosis, inflammatory have been described years. Recently, several novel forms namely, mitoptosis, paraptosis, immunogenic entosis, methuosis, parthanatos, ferroptosis, autosis, alkaliptosis, oxeiptosis, cuproptosis, erebosis, discovered advanced our understanding its complexity. In this review, we provide historical overview discovery characterization highlight their diversity We also briefly discuss regulatory mechanisms underlying each type implications various physiological pathological contexts. This review provides comprehensive can leveraged develop therapeutic strategies for diseases.

Language: Английский

---

Hypoxia: The Cornerstone of Glioblastoma

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(22), P. 12608 - 12608

Published: Nov. 22, 2021

Glioblastoma is the most aggressive form of brain tumor in adults and characterized by presence hypervascularization necrosis, both caused a hypoxic microenvironment. In this review, we highlight that hypoxia-induced factor 1 (HIF-1), main activated hypoxia, an important driver progression GB patients. HIF-1α transcription regulated or absence O2. The expression HIF-1 has been related to high-grade gliomas behavior. promotes via activation angiogenesis, immunosuppression, metabolic reprogramming, promoting cell invasion survival. Moreover, GB, not solely modulated oxygen but also oncogenic signaling pathways, such as MAPK/ERK, p53, PI3K/PTEN. Therefore, inhibition hypoxia pathway could represent treatment alternative disease with very few therapy options. Here, review roles inhibitors have studied thus far, aim shedding light on devastating disease.

Language: Английский

---

Going circular: history, present, and future of circRNAs in cancer

Oncogene, Journal Year: 2023, Volume and Issue: 42(38), P. 2783 - 2800

Published: Aug. 16, 2023

Abstract To date, thousands of highly abundant and conserved single-stranded RNA molecules shaped into ring structures (circRNAs) have been identified. CircRNAs are multifunctional that shown to regulate gene expression transcriptionally post-transcriptionally exhibit distinct tissue- development-specific patterns associated with a variety normal disease conditions, including cancer pathogenesis. Over the past years, due their intrinsic stability resistance ribonucleases, particular attention has drawn use as reliable diagnostic prognostic biomarkers in diagnosis, treatment, prevention. However, there some critical caveats utility clinic. Their circular shape limits annotation complete functional elucidation is lacking. This makes detection biomedical application still challenging. Herein, we review current knowledge circRNA biogenesis function, involvement tumorigenesis potential cancer-targeted therapy.

Language: Английский

---

HK1 from hepatic stellate cell–derived extracellular vesicles promotes progression of hepatocellular carcinoma

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(10), P. 1306 - 1321

Published: Oct. 3, 2022

Extracellular vesicles play crucial roles in intercellular communication the tumor microenvironment. Here we demonstrate that hepatic fibrosis, TGF-β stimulates palmitoylation of hexokinase 1 (HK1) stellate cells (HSCs), which facilitates secretion HK1 via large extracellular a TSG101-dependent manner. The vesicle is hijacked by hepatocellular carcinoma (HCC) cells, leading to accelerated glycolysis and HCC progression. In HSCs, nuclear receptor Nur77 transcriptionally activates expression depalmitoylase ABHD17B inhibit palmitoylation, consequently attenuating release. However, TGF-β-activated Akt functionally represses inducing phosphorylation degradation. We identify small molecule PDNPA binds generate steric hindrance block targeting, thereby disrupting Akt-mediated degradation preserving inhibition Together, this study demonstrates an overlooked function upon its release from HSCs highlights as candidate compound for inhibiting

Language: Английский

---