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"Wang, Miao"
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Membrane-associated RING-CH protein (MARCH8) is a novel glycolysis repressor targeted by miR-32 in colorectal cancer
Background
Colorectal cancer (CRC) is the third most common cancer and leading cause of cancer-related deaths worldwide. Aberrant cellular metabolism is a hallmark of cancer cells, and disturbed metabolism showed clinical significance in CRC. The membrane-associated RING-CH 8 (MARCH8) protein, the first MARCH E3 ligase, plays an oncogenic role and serves as a prognostic marker in multiple cancers, however, the role of MARCH8 in CRC is unclear. In the present study, we aimed to investigate the biomarkers and their underlying mechanism for CRC.
Method
In this study, we first examined the function of MARCH8 in CRC by analysing public database. Besides, we performing gene silencing studies and generating cellular overexpression and xenograft models. Then its protein substrate was identified and validated. In addition, the expression of MARCH8 was investigated in tissue samples from CRC patients, and the molecular basis for decreased expression was analysed.
Results
Systematic analysis reveals that MARCH8 is a beneficial prognostic marker in CRC. In CRC, MARCH8 exhibited tumor-suppressive activity both in vivo and in vitro. Furthermore, we found that MARCH8 is negatively correlated with hexokinase 2 (HK2) protein in CRC patients. MARCH8 regulates glycolysis and promotes ubiquitination-mediated proteasome degradation to reduces HK2 protein levels. Then HK2 inhibitor partially rescues the effect of MARCH8 knockdown in CRC
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Poised chromatin and elevated miR-32 repressed MARCH8 expression.
Conclusion
In summary, we propose that in CRC, poised chromatin and miR-32 decrease the expression of MARCH8, further bind and add ubiquitin, induce HK2 degradation, and finally repress glycolysis to promote tumor suppressors in CRC.
Journal Article
China's domestic and international migration development
This book offers the most comprehensive, up-to-date assessment of China's domestic and international migration. Restructuring economic development requires large numbers of educated and skilled talents, but this effort comes at a time when the size of China's domestic workforce is shrinking. In response, both national and regional governments in China have been keen to encourage overseas Chinese talents and professionals to return to the country. Meanwhile, the Chinese government has initiated a number of policies to attract international highly-skilled talents and enhance the country's competitiveness, and some Chinese policies have started attracting foreign talents, who are coming to the country to work, and even to stay. Since Chinese policies, mechanisms, and administration efforts to attract and retain skilled domestic or overseas talents are helping to reshape China's economy and are significantly affecting the cooperation on migration and talent mobility, these aspects, in addition to being of scholarly and research interest, hold considerable commercial potential.
Book
Hypoxia‐responsive ERFs involved in postdeastringency softening of persimmon fruit
Summary Removal of astringency by endogenously formed acetaldehyde, achieved by postharvest anaerobic treatment, is of critical importance for many types of persimmon fruit. Although an anaerobic environment accelerates de‐astringency, it also has the deleterious effect of promoting excessive softening, reducing shelf life and marketability. Some hypoxia‐responsive ethylene response factors (ERFs) participate in anaerobic de‐astringency, but their role in accelerated softening was unclear. Undesirable rapid softening induced by high CO2 (95%) was ameliorated by adding the ethylene inhibitor 1‐MCP (1 μL/L), resulting in reduced astringency while maintaining firmness, suggesting that CO2‐induced softening involves ethylene signalling. Among the hypoxia‐responsive genes, expression of eight involved in fruit cell wall metabolism (Dkβ‐gal1/4, DkEGase1, DkPE1/2, DkPG1, DkXTH9/10) and three ethylene response factor genes (DkERF8/16/19) showed significant correlations with postdeastringency fruit softening. Dual‐luciferase assay indicated that DkERF8/16/19 could trans‐activate the DkXTH9 promoter and this interaction was abolished by a mutation introduced into the C‐repeat/dehydration‐responsive element of the DkXTH9 promoter, supporting the conclusion that these DkERFs bind directly to the DkXTH9 promoter and regulate this gene, which encodes an important cell wall metabolism enzyme. Some hypoxia‐responsive ERF genes are involved in deastringency and softening, and this linkage was uncoupled by 1‐MCP. Fruit of the Japanese cultivar ‘Tonewase’ provide a model for altered anaerobic response, as they lost astringency yet maintained firmness after CO2 treatment without 1‐MCP and changes in cell wall enzymes and ERFs did not occur.
Journal Article
The impact of the endoplasmic reticulum protein-folding environment on cancer development
Key Points
Defective protein folding in the endoplasmic reticulum (ER) and unfolded protein response (UPR) activation are documented in many human cancer types, which is attributed to both intrinsic and extrinsic factors.
UPR activation is a vital step for oncogenic transformation, as UPR signalling molecules interact with well-established oncogene and tumour suppressor gene networks to modulate their function during cancer development.
Conditions of low nutrient supply (for example, glucose or oxygen deprivation), as well as excess nutrients (fatty acids, cholesterol and glucose) induce ER stress and UPR activation. UPR induction promotes cancer cell survival through induction of autophagy and adaptation to the stressful microenvironment.
ER stress and UPR activation possibly promote cancer development and progression through modulating inflammatory responses.
The UPR is indispensable in cells in the tumour microenvironment to either promote or inhibit cancer progression.
Targeting the UPR, through single or combination therapy, provides a promising therapeutic approach for many different cancers.
The unfolded protein response (UPR) is an important pro-survival pathway that is often activated in tumour cells owing to endoplasmic reticulum stress that is caused by both intrinsic and extrinsic factors. Wang and Kaufman discuss the mechanisms of UPR activation in tumour cells, the importance of this pathway to cancer development and targeting strategies for therapeutic intervention.
The endoplasmic reticulum (ER) is an essential organelle in eukaryotic cells for the storage and regulated release of calcium and as the entrance to the secretory pathway. Protein misfolding in the ER causes accumulation of misfolded proteins (ER stress) and activation of the unfolded protein response (UPR), which has evolved to maintain a productive ER protein-folding environment. Both ER stress and UPR activation are documented in many different human cancers. In this Review, we summarize the impact of ER stress and UPR activation on every aspect of cancer and discuss outstanding questions for which answers will pave the way for therapeutics.
Journal Article
TRIM21 inhibits irradiation-induced mitochondrial DNA release and impairs antitumour immunity in nasopharyngeal carcinoma tumour models
Although radiotherapy can promote antitumour immunity, the mechanisms underlying this phenomenon remain unclear. Here, we demonstrate that the expression of the E3 ubiquitin ligase, tumour cell-intrinsic tripartite motif-containing 21 (TRIM21) in tumours, is inversely associated with the response to radiation and CD8
+
T cell-mediated antitumour immunity in nasopharyngeal carcinoma (NPC). Knockout of TRIM21 modulates the cGAS/STING cytosolic DNA sensing pathway, potentiates the antigen-presenting capacity of NPC cells, and activates cytotoxic T cell-mediated antitumour immunity in response to radiation. Mechanistically, TRIM21 promotes the degradation of the mitochondrial voltage-dependent anion-selective channel protein 2 (VDAC2) via K48-linked ubiquitination, which inhibits pore formation by VDAC2 oligomers for mitochondrial DNA (mtDNA) release, thereby inhibiting type-I interferon responses following radiation exposure. In patients with NPC, high TRIM21 expression was associated with poor prognosis and early tumour relapse after radiotherapy. Our findings reveal a critical role of TRIM21 in radiation-induced antitumour immunity, providing potential targets for improving the efficacy of radiotherapy in patients with NPC.
The molecular mechanisms determining the response to radiotherapy remain incompletely understood. Here, the authors demonstrate that the E3 ubiquitin ligase and intracellular Fc receptor, TRIM21, impairs CD8
+
T cell responses in nasopharyngeal carcinoma tumour models following ionizing radiation.
Journal Article
Phylogeny and evolution of hemipteran insects based on expanded genomic and transcriptomic data
Background
Hemiptera is the fifth species-rich order of insects and the most species-rich order of hemimetabolous insects, including numerous insect species that are of agricultural or medical significance. Despite much effort and recent advance in inferring the Hemiptera phylogeny, some high-level relationships among superfamilies remain controversial.
Results
We sequenced the genomes of 64 hemipteran species from 15 superfamilies and the transcriptomes of two additional scale insect species, integrating them with existing genomic and transcriptomic data to conduct a comprehensive phylogenetic analysis of Hemiptera. Our datasets comprise an average of 1625 nuclear loci of 315 species across 27 superfamilies of Hemiptera. Our analyses supported Cicadoidea and Cercopoidea as sister groups, with Membracoidea typically positioned as the sister to Cicadoidea + Cercopoidea. In most analyses, Aleyrodoidea was recovered as the sister group of all other Sternorrhyncha. A sister-group relationship was supported between Coccoidea and Aphidoidea + Phylloxeroidea. These relationships were further supported by four-cluster likelihood mapping analyses across diverse datasets. Our ancestral state reconstruction indicates phytophagy as the primary feeding strategy for Hemiptera as a whole. However, predation likely represents an ancestral state for Heteroptera, with several phytophagous lineages having evolved from predatory ancestors. Certain lineages, like Lygaeoidea, have undergone a reversal transition from phytophagy to predation. Our divergence time estimation placed the diversification of hemipterans to be between 60 and 150 million years ago.
Conclusions
By expanding phylogenomic taxon sampling, we clarified the superfamily relationships within the infraorder Cicadomorpha. Our phylogenetic analyses supported the sister-group relationship between the superfamilies Cicadoidea and Cercopoidea, and the superfamily Membracoidea as the sister to Cicadoidea + Cercopoidea. Our divergence time estimation supported the close association of hemipteran diversification with the evolutionary success and adaptive radiation of angiosperms during the Cretaceous period.
Journal Article
Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies
The gut microbiota have long been recognized to play a key role in human health and disease. Currently, several lines of evidence from preclinical to clinical research have gradually established that the gut microbiota can modulate antitumor immunity and affect the efficacy of cancer immunotherapies, especially immune checkpoint inhibitors (ICIs). Deciphering the underlying mechanisms reveals that the gut microbiota reprogram the immunity of the tumor microenvironment (TME) by engaging innate and/or adaptive immune cells. Notably, one of the primary modes by which the gut microbiota modulate antitumor immunity is by means of metabolites, which are small molecules that could spread from their initial location of the gut and impact local and systemic antitumor immune response to promote ICI efficiency. Mechanistic exploration provides novel insights for developing rational microbiota-based therapeutic strategies by manipulating gut microbiota, such as fecal microbiota transplantation (FMT), probiotics, engineered microbiomes, and specific microbial metabolites, to augment the efficacy of ICI and advance the age utilization of microbiota precision medicine.
Journal Article
Reflection of rightward moving shocks of the first and second families over a steady oblique shock wave
The reflection of rightward moving shocks (RMSs) belonging to the first and second families, over an initially steady oblique shock wave (SOSW) produced by a wedge, is studied in this paper. Various possible combinations of primary reflection (reflection at the intersection point of the RMS and the SOSW) and secondary reflection (reflection, on the wedge, of reflected shock waves of the primary reflection) are identified and the transition conditions are studied. For an RMS of the first family, the shock reflection problem can be shown to be equivalent to a shock interference problem. If the wedge angle is large, then the problem is equivalent to a shock interaction problem with two incident shock waves of the same family so that we have type VI, type V and type IV shock interferences. Interestingly, when the wedge angle is small enough, deflection angle reversal is observed for the SOSW so that the right part of the SOSW can no longer be regarded as one incident shock wave. It is now the left part of the SOSW that becomes one incident shock wave. As a result, for a small wedge angle, type I or type II shock interference is observed. If the RMS belongs to the second family, then the primary reflection may have regular and Mach reflections, and one reflected shock of this primary reflection reflects over the wall as another pseudo-steady shock reflection, while the other reflected shock wave may be smooth or have a kink or a triple point, as in single, transitional and double Mach reflection of pseudo-steady shock reflection.
Journal Article
The effects of peer overqualification on dualistic work passion through the sequential mediation of perceived competitive climate and job anxiety
The phenomenon of overqualification is widespread and profoundly impacts employees’ work attitudes. While existing studies have explored overqualification, limited research has focused on the effects of peer overqualification on employees’ dualistic work passion through affective and cognitive mechanisms. Grounded in the theoretical framework of conservation of resource theory as well as cognitive-affective processing system theory, this study examines the relationship between peer overqualification and the production of employees’ dualistic work passion. It analyzes the mediating role of a perceived competitive climate and job anxiety. Utilizing a sample of 532 employees from China, this study finds that peer overqualification stimulates employees’ obsessive work passion and negatively impacts their harmonious work passion. Perceived competitive climate and job anxiety play a chain mediation role in the positive relationship between peer overqualification and obsessive work passion and the negative relationship between peer overqualification and harmonious work passion. This study broadens the theoretical perspectives on peer overqualification, enriches research on the determinants of dualistic work passion, and offers managerial implications for enhancing employees’ work passion.
Journal Article