RESUMO
Cancer is a type of malignant affliction threatening human health worldwide; however, the molecular mechanism of cancer pathogenesis remains to be elusive. The oncogenic hedgehog (Hh) pathway is a highly evolutionarily conserved signaling pathway in which the hedgehog-Patched complex is internalized to cellular lysosomes for degradation, resulting in the release of Smoothened inhibition and producing downstream intracellular signals. Noncoding RNAs (ncRNAs) with diversified regulatory functions have the potency of controlling cellular processes. Compelling evidence reveals that Hh pathway, ncRNAs, or their crosstalk play complicated roles in the initiation, metastasis, apoptosis and drug resistance of cancer, allowing ncRNAs related to the Hh pathway to serve as clinical biomarkers for targeted cancer therapy. In this review, we attempt to depict the multiple patterns of ncRNAs in the progression of malignant tumors via interactions with the Hh crucial elements in order to better understand the complex regulatory mechanism, and focus on Hh associated ncRNA therapeutics aimed at boosting their application in the clinical setting.
Assuntos
Proteínas Hedgehog , Neoplasias , Apoptose , Proteínas Hedgehog/genética , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , RNA não Traduzido/genética , Transdução de Sinais/fisiologiaRESUMO
The eukaryotic translation initiation factor 4 (EIF4) family is a major contributor to the recruitment of mRNAs to ribosomes during the initial translation stage in eukaryotes, whose dysregulation either allows for cancer transformation or prevents disordered cancerous cell growth. Circular RNAs (circRNAs), which exhibit distinctive structures and are widely expressed in eukaryotes, are anticipated to be clinical diagnostic biomarkers for cancer therapy. There is considerable evidence that EIF4s can influence the biogenesis, transport, and function of circRNAs and, in turn, circRNAs can control the expressions of EIF4s through certain molecular pathways. Herein, we primarily review the emerging studies of the EIF4 family and pinpoint the roles of dysregulated EIF4s in cancer. We also evaluate the patterns of intricate interactions between circRNAs and EIF4s and discuss the potential utility of circRNA-based therapeutics targeting EIF4s in clinical cancer research.
Assuntos
Neoplasias , RNA Circular , Humanos , RNA Circular/genética , RNA/metabolismo , RNA Mensageiro , Neoplasias/genética , Neoplasias/terapia , Fatores de Iniciação de Peptídeos , BiomarcadoresRESUMO
Alternative splicing controls gene expression at the transcriptional level, producing structurally and functionally distinct protein heterodimers. Aberrant alternative splicing greatly affects cell development and plays an important role in the invasion and metastasis of many types of cancer. Recently, it has been shown that alternative splicing can alter the tumor microenvironment and regulate processes such as remodeling, immunity, and inflammation in the tumor microenvironment. However, there is no comprehensive literature review of the complex relationship between alternative splicing and the tumor microenvironment. Therefore, this review aims to collect all the latest data on this topic and provide a new perspective on the therapeutic and potential prognostic markers of cancer.
Assuntos
Processamento Alternativo , Neoplasias , Humanos , Neoplasias/genética , Diferenciação Celular , Inflamação , Microambiente Tumoral/genéticaRESUMO
The copper matrix composites were prepared by spark plasma sintering (SPS). The current-carrying friction and wear tests were carried out on a self-made HST-100 high-speed current-carrying friction and wear tester, and the effect of the graphite content on the current-carrying friction and wear properties of the composite material was studied. The results show that with an increase in graphite content, the average friction coefficient and wear rate of the two materials decreased significantly, the fluctuation amplitude of the friction coefficient was also significantly reduced, and the average friction coefficient of copper-coated graphite composite with graphite content of 10 wt.% was 0.100; when the graphite content was the same and more than 5.0 wt.%, the average friction coefficient and wear rate of copper-graphite composites were slightly higher than copper-copper-coated graphite composites; the current-carrying efficiency and current-carrying stability of the copper matrix composite were obviously higher than that of copper material; there was a mechanical wear area and arc erosion area on the wear surface of the composites, with the increase in graphite content, the adherence and the tear of the mechanical wear area weakened, the rolling, plastic deformation increased, and the surface roughness decreased obviously. The surface roughness of the wear surface of copper-copper-coated graphite composites with graphite content of 10 wt.% was 3.17 µm. The forms of arc erosion included melting and splashing, and were mainly distributed in the friction exit area.
RESUMO
Copper-graphite composites were prepared by spark plasma sintering (SPS) with copper powder and copper-coated graphite powder. The effect of particle size of raw material powder on the current-carrying friction properties of copper-graphite composites was studied. The results show that the friction coefficient of the composites decreased with the decrease of the particle size of copper-coated graphite powder, the friction coefficient of the composites increased with the decrease of the particle size of the copper powder, the wear rate of the composites increased with the decrease of the particle size of the copper-coated graphite powder, and the wear rate of the composites increased significantly with the decrease of the particle size of the copper-coated graphite powder. The current carrying properties of composites with different particle size ratios and QCr0.5 pairs are good and fluctuate little. The current-carrying friction properties of 150 µm copper powder and 75 µm copper-coated graphite powder were found to be the best. The wear surface could be divided into mechanical wear area and arc erosion area. The main area of arc erosion was less than 15% of the total area, and it was mainly distributed in the friction outlet area. The main forms of mechanical wear included furrow, rolling deformation, cold welding, and tearing, among other forms. Graphite film was formed on the surface. The surface quality of the composite prepared by 150 µm copper powder and 75 µm copper-coated graphite powder was the best, the Sa was 3.22 µm, rolling deformation was the most adequate, no large tear pit and furrow appeared, and the carbon content on the worn surface was much higher than that in the composite. The behavior of arc erosion was mainly melting and splashing, and the particle size of the original powder had little effect on it.