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The Mechanism diagram, miR-574-3p stabilized and promoted the HIF-1α expression in GC cells by dampening the CUL2 level. Meanwhile, the stable HIF-1α enhanced the expression of Vimentin and Snail, and attenuated the E-cadherin level, thus activating the EMT
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Background
Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. MicroRNAs (miRNAs) have been widely validated as potential biomarkers for cancer treatment and diagnosis.AimsThis paper intends to study the effect and specific mechanism of miR-574-3p/CUL2 axis in GC.Methods
The miR-574-3p expression in GC tissues and cel...
Citations
... Zhiwu et al. showed that miR-574-3p was overexpressed in GC tissues and cells. miR-574-3p targeted CUL2 to increase HIF-1α expression, affecting GC progression [50]. The TCGA database have not shown increased miR-574 values in GC. ...
Introduction: Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Although the incidence is decreasing in developed countries, treatment results are still unsatisfactory. The standard treatment for locally advanced gastric cancer (LAGC) is gastrectomy with perioperative chemotherapy. Aim: Assessment of selected microRNAs (miRNAs) in chemoresistance in archival material from LAGC. Material and method: The research group consisted of archival material from 10 patients with LAGC. Histological material from each patient was used from a biopsy performed during gastroscopy and after surgery preceded by 4 cycles of neoadjuvant chemotherapy (NAC) according to the FLOT or FLO regimen. The expression of selected miRNAs was assessed in the tissue material, such as miRNA-21-3p, miRNA-21-5p, miRNA-106a-5p, miRNA-122-3p, miRNA-122-5p, miRNA-143-3p, miRNA-143-5p, miRNA-203a-3p, miRNA-203-5p, miRNA-551b-3p, miRNA-551b-5p and miRNA-574-3p. miRNA expression was assessed by quantitative chain reaction polymerase reverse transcriptase (qRT-PCR). The response to NAC was assessed by computed tomography of the abdomen, chest and histopathology after gastrectomy. The statistical analyses were performed using GraphPad Prism 9.The significance limit was set at p
... Research has demonstrated that stabilizing HIF by inhibiting CUL2 neddylation can protect mucosal inflammatory responses [32]. MicroRNA-574-3p Regulates HIF-α Isoforms Promoting Gastric Cancer Epithelial-Mesenchymal Transition via Targeting CUL2 [33]. Studies have shown that NLRC5 plays a role in limiting dengue virus infection by promoting the autophagic degradation of viral NS3 through the E3 ligase CUL2. ...
Background:
As a member of the Cullin family, Cullin2 (CUL2) is involved in the development and spread of different types of cancers. However, the precise role of CUL2 in human cancer remains largely elusive.
Methods:
In this study, various databases were applied to observe the CUL2 expression. Kaplan-Meier and Spearman correlation analyses were employed to investigate the potential links between CUL2 level, patient prognosis, and the infiltration of immune cells. In addition, the association between CUL2 and the efficacy of immunotherapy in an immunotherapy cohort was investigated. Moreover, the expression and distribution of CUL2 in cells were observed using the Human Protein Atlas (THPA) database. Finally, clinical tissue specimens and in vitro function assays were conducted to validate the expressions and effects of CUL2 on the biological functions in hepatocellular carcinoma (HCC) cells.
Results:
While there are variations in CUL2 expression across different organs and cell types, it is notably upregulated in a majority of tumor tissues. In addition, CUL2 gene mutations are common in multiple cancers with low mutation rates and CUL2 is closely related to the prognosis of some cancer's patients, some immune regulatory factors, TMB, MSI, MMR genes, and DNA methylation. Further, our results found that downregulating CUL2 inhibits the proliferation, and migration abilities.
Conclusions:
The expression of CUL2 has an impact on the prognosis of various tumors, and this correlation is particularly noteworthy due to its significant association with the infiltration of immune cells within tumors. CUL2 was an oncogene contributing to the progression of HCC.
... Ji and colleagues demonstrated that expression of miR-574-3p is elevated in gastric cancer tissues. The forced expression of miR-574-3p resulted in the acceleration of cell proliferation, motility, and EMT of gastric cancer cells [73]. The observed inhibitory effect of miR-574-3p was found to be mediated through targeting cullin 2 (CUL2), a scaffold protein that has been known to suppress HIF-1α expression. ...
... The observed inhibitory effect of miR-574-3p was found to be mediated through targeting cullin 2 (CUL2), a scaffold protein that has been known to suppress HIF-1α expression. miR-574-3p promoted the expression of HIF-1α by decreasing CUL2 to stimulate EMT and metastasis [73]. HIF-1α and miRNA can form a positive feedback loop to modulate the expression of each other. ...
The hypoxic environment is prominently witnessed in most solid tumors and is associated with the promotion of cell proliferation, epithelial-mesenchymal transition (EMT), angiogenesis, metabolic reprogramming, therapeutic resistance, and metastasis of tumor cells. All the effects are mediated by the expression of a transcription factor hypoxia-inducible factor-1α (HIF-1α). HIF-1α transcriptionally modulates the expression of genes responsible for all the aforementioned functions. The stability of HIF-1α is regulated by many proteins and non-coding RNAs (ncRNAs). In this article, we have critically discussed the crucial role of ncRNAs [such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), Piwi-interacting RNAs (piRNAs), and transfer RNA (tRNA)-derived small RNAs (tsRNAs)] in the regulation of stability and expression of HIF-1α. We have comprehensively discussed the molecular mechanisms and relationship of HIF-1α with each type of ncRNA in either promotion or repression of human cancers and therapeutic resistance. We have also elaborated on ncRNAs that are in clinical examination for the treatment of cancers. Overall, the majority of aspects concerning the relationship between HIF-1α and ncRNAs have been discussed in this article.
A recent focus on the regulatory roles of non-coding RNAs has widened our knowledge of their biological functions. These regulatory roles inherently exist owing to their unique structures. Cancer research is increasingly based on the roles of multiple non-coding RNAs. Crucial to explore are the major cancer hallmarks that combine to bring about an aggressive phenotype in cancer cells. Epithelial-to-mesenchymal transition (EMT) contributes towards an increasing metastatic potential in cancer cells, additionally leading to the domination of cancer stem cells (CSCs), which have a higher propensity to seed secondary tumors. An ever aggressively growing tumor gains a survival advantage by reprogramming its metabolism and becomes therapy resistant. Tumor hypoxia is centric to an aggressive cancer phenotype along with other physiological factors. Literature has shown how hypoxia could contribute towards EMT in cancer. This chapter focuses on the crucial role of several non-coding RNAs that mediate hypoxia-driven EMT in multiple cancers. We aim to discuss the structural and functional aspects of these regulatory non-coding RNAs. Importantly, we focus on the cell signaling pathway crosstalk, mediated by ncRNAs in multiple cancers, and describe how different pathways that are crucial to both EMT and hypoxia converge onto some important molecular players. Interestingly, several ncRNAs have been implicated as novel biomarkers and therapeutic targets. A detailed understanding of the ncRNAs regulating hypoxia-driven EMT would help enable future studies of these phenomena.
Purpose of Review
Rapidly evolving treatment paradigms of coronavirus disease 2019 (COVID-19) introduce challenges for clinicians to keep up with the pace of published literature and to critically appraise the voluminous data produced. This review summarizes the clinical evidence from key studies examining the place of therapy of recommended drugs and management strategies for COVID-19.
Recent Findings
The global magnitude and duration of the pandemic have resulted in a flurry of interventional treatment trials evaluating both novel and repurposed drugs targeting various aspects of the viral life cycle. Additionally, clinical observations have documented various stages or phases of COVID-19 and underscored the importance of timing for the efficacy of studied therapies. Since the start of the COVID-19 pandemic, many observational, retrospective, and randomized controlled studies have been conducted to guide management of COVID-19 using drug therapies and other management strategies. Large, randomized, or adaptive platform trials have proven the most informative to guide recommended treatments to-date. Antimicrobial stewardship programs can play a pivotal role in ensuring appropriate use of COVID-19 therapies based on evolving clinical data and limiting unnecessary antibiotics given low rates of co-infection.
Summary
Given the rapidly evolving medical literature and treatment paradigms, it is recommended to reference continuously updated, curated guidelines from national and international sources. While the drugs and management strategies mentioned in this review represent the current state of recommendations, many therapies are still under investigation to further define optimal COVID-19 treatment.
