ExosomalmicroRNA let-7c-5p enhances cell malignant characteristics by inhibiting TAGLN in oral cancer

Background:Oral cancer,a malignancy that is prevalent worldwide,is often diagnosed at an advanced stage.MicroRNAs(miRNAs)in circulating exosomes have emerged as promising cancer biomarkers.The role of miRNA let-7c-5p in oral cancer remains underexplored,and its potential involvement in tumorigenesis warrants comprehensive investigation.Methods:Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA content.Isolation of the exosomes was confirmed through transmission electron microscopy.Quantitative PCR was used to assess the miRNA profiles.The effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability,migration,and invasion were analyzed via CCK-8 and Transwell assays.Moreover,we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target genes.Results:let-7c-5p was upregulated in serumderived exosomes of patients with oral cancer.Overexpression of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative,migratory,and invasive capacities,and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell invasiveness.Exosomal mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived exosomes.We further identified TAGLN as a direct target of let-7c-5p,which has been implicated in modulating the oncogenic potential of oral cancer cells.Overexpression of TAGLN reverses the promoting role of let-7c-5p on oral cancer cells.Conclusion:Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression,highlighting its potential as a diagnostic and therapeutic strategy.

Bio-Manufacturing Research Center at Tsinghua University

Overview and research infrastructure As one of the leading laboratories in the interdisciplinary field of additive manufacturing and bio-3D printing,the Bio-Manufacturing Center at Tsinghua University is highly dedicated to conducting cutting-edge research in the emerging field of bio-manufacturing.The latter is comprised of research involving biomaterials,living cells,proteins,and/or other biological compounds as basic building blocks to fabricate biomimetic structures,in vitro functional biological models and/or cellular systems with application to tissue engineering,regenerative medicine,disease pathogenesis,drug screening,and tissue/organ-on-a-chip.

Cancer cachexia:Focus on cachexia factors and inter-organ communication

Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs,which is mediated by cancer cachexia factors.Cancer cachexia factors,being the general name of inflammatory factors,circulating proteins,metabolites,and microRNA secreted by tumor or host cells,play a role in secretory or other organs and mediate complex signal communication between organs during cancer cachexia.Cancer cachexia factors are also a potential target for the diagnosis and treatment.The pathogenesis of cachexia is unclear and no clear effective treatment is available.Thus,the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently needed.From the point of signal communication between organs mediated by cancer cachexia factors,finding a deeper understanding of the pathogenesis,diagnosis,and treatment of cancer cachexia is of great significance to improve the level of diagnosis and treatment.This review begins with cancer cachexia factors released during the interaction between tumor and host cells,and provides a comprehensive summary of the pathogenesis,diagnosis,and treatment for cancer cachexia,along with a particular sight on multi-organ signal communication mediated by cancer cachexia factors.This summary aims to deepen medical community’s understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.

Drug repurposing for cancer therapy

Cancer,a complex and multifactorial disease,presents a significant challenge to global health.Despite significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic strategy.However,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer therapeutics.One promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved drugs.Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety profiles.In light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat cancer.We describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment.In addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery.We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen.To conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

Role of the gut microbiota in anticancer therapy:from molecular mechanisms to clinical applications

In the past period,due to the rapid development of next-generation sequencing technology,accumulating evidence has clarified the complex role of the human microbiota in the development of cancer and the therapeutic response.More importantly,available evidence seems to indicate that modulating the composition of the gut microbiota to improve the efficacy of anti-cancer drugs may be feasible.However,intricate complexities exist,and a deep and comprehensive understanding of how the human microbiota interacts with cancer is critical to realize its full potential in cancer treatment.The purpose of this review is to summarize the initial clues on molecular mechanisms regarding the mutual effects between the gut microbiota and cancer development,and to highlight the relationship between gut microbes and the efficacy of immunotherapy,chemotherapy,radiation therapy and cancer surgery,which may provide insights into the formulation of individualized therapeutic strategies for cancer management.In addition,the current and emerging microbial interventions for cancer therapy as well as their clinical applications are summarized.Although many challenges remain for now,the great importance and full potential of the gut microbiota cannot be overstated for the development of individualized anti-cancer strategies,and it is necessary to explore a holistic approach that incorporates microbial modulation therapy in cancer.

NAT 10 promotes gastric cancer metastasis via N4-acetylated COL5A1

Dear Editor,Gastric cancer(GC)is among the most prevalent gastrointestinal malignancies.The occurrence of local deep infiltration or distant metastasis in GC is commonly associated with weak treatment and poor prognosis.1 Although,N4-Acetylcytidine(ac4C)represents one of the extensive chemical modifications in mRNAs that plays a pivotal role in modulating mRNA stability and the mRNA translation process(Fig.1b).

Activating transcription factor 3,glucolipid metabolism,and metabolic diseases

Lipids and glucose exert many essential physiological functions,such as providing raw materials or energy for cellular biosynthesis,regulating cell signal transduction,and maintaining a constant body temperature.Dysregulation of lipid and glucose metabolism can lead to glucolipid metabolic disorders linked to various metabolic diseases,such as obesity,diabetes,and cardiovascular disease.Therefore,intervention in glucolipid metabolism is a key therapeutic strategy for the treatment of metabolic diseases.Activating transcription factor 3(ATF3)is a transcription factor that acts as a hub of the cellular adaptive-response network and plays a pivotal role in the regulation of inflammation,apoptosis,DNA repair,and oncogenesis.Emerging evidence has illustrated the vital roles of ATF3 in glucolipid metabolism.ATF3 inhibits intestinal lipid absorption,enhances hepatic triglyceride hydrolysis and fatty acid oxidation,promotes macrophage reverse cholesterol transport,and attenuates the progression of western diet-induced nonalcoholic fatty liver disease and atherosclerosis.In addition to its role in lipid metabolism,ATF3 has also been identified as an important regulator of glucose metabolism.Here,we summarize the recent advances in the understanding of ATF3,mainly focusing on its role in glucose and lipid metabolism and potential therapeutic implications.

Critical involvement of lysyl oxidase in seizure-induced neuronal damage through ERK-Alox5-dependent ferroptosis and its therapeutic implications

Recent insights collectively suggest the important roles of lysyl oxidase(LysOX)in the pathological processes of several acute and chronic neurological diseases,but the molecular regulatory mechanisms remain elusive.Herein,we explore the regulatory role of LysOX in the seizure-induced ferroptotic cell death of neurons.Mechanistically,LysOX promotes ferroptosis-associated lipid peroxidation in neurons via activating extracellular regulated protein kinase(ERK)-dependent 5-lipoxygenase(Alox5)signaling.In addition,overexpression of LysOX via adeno-associated viral vector(AAV)-based gene transfer enhances ferroptosis sensitivity and aggravates seizure-induced hippocampal damage.Our studies show that pharmacological inhibition of LysOX withβ-aminopropionitrile(BAPN)significantly blocks seizure-induced ferroptosis and thereby alleviates neuronal damage,while the BAPN-associated cardiotoxicity and neurotoxicity could further be reduced through encapsulation with bioresponsive amorphous calcium carbonate-based nanocarriers.These findings unveil a previously unrecognized LysOX-ERK-Alox5 pathway for ferroptosis regulation during seizure-induced neuronal damage.Suppressing this pathway may yield therapeutic implications for restoring seizure-induced neuronal injury.

The arsenal of TP53 mutants therapies:neoantigens and bispecific antibodies

A recent research published in Science by Hsiue et al.1 introduced a CD3-targeting bispecific antibody that can bind to tumor cells by recognizing mutation-associated neoantigens and activate T cell-mediated tumor killing by binding to CD3.The tumor suppressor gene TP53 is the most commonly mutated gene in various cancers.

Cell perturbation in choroid plexus and cortex aiding COVID-19 neurological symptoms

Patients with coronavirus disease 2019 (COVID-19) often succumb to neurological manifestations such as loss of smell, headache, disturbed consciousness, seizure, and stroke. In a recent paper published in Nature, Yang et al.[1] reported substantial cellular perturbations in the choroid plexus and cortex, notably an infiltration of peripheral T cells into the parenchyma and microglial activation and astrogliosis with distinct transcriptional profiles. These findings provide a complex view of the cellular and molecular processes underlying COVID-19-related neurological abnormalities.