A controlled random gene perturbation method identifies ARPC1B gene as a key regulator of cancer metastasis

The discovery of clinically useful targets to treat specific pathological conditions can provide novel therapeutic approaches.To unbiasedly identify key genes related to tumor metastasis,we developed a random gene perturbation method using a piggyBac transposon system under the control of a doxycycline regulated promoter.Using this random gene perturbation method and utilizing a mouse model of metastatic pancreatic cancer,we identified genes dysregulated in metastasized cells from a random mutagenesis library after multiple rounds of in vivo selection.Analysis of these metastasized clones revealed the downregulation of ARPC1B gene.Our further mechanistic studies revealed that ARPC1B gene and its closely related gene ARPC1A worked in a regulatory loop to control tumor metastasis.These findings validate that piggyBac transposon mediated random gene perturbation is a powerful tool to investigate the functional relevance of novel genes and the ARPC1A/B axis is a potential key regulator of tumor metastasis.

Interactions between the lung microbiome and host immunity in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease(COPD)is a common chronic respiratory disease and the third leading cause of death worldwide.Developments in next-generation sequencing technology have improved microbiome analysis,which is increasingly recognized as an important component of disease management.Similar to the gut,the lung is a biosphere containing billions of microbial communities.The lung microbiome plays an important role in regulating and maintaining the host immune system.The microbiome composition,metabolites of microorganisms,and the interactions between the lung microbiome and the host immunity profoundly affect the occurrence,development,treatment,and prognosis of COPD.In this review,we drew comparisons between the lung microbiome of healthy individuals and that of patients with COPD.Furthermore,we summarize the intrinsic interactions between the host and the overall lung microbiome,focusing on the underlying mechanisms linking the microbiome to the host innate and adaptive immune response pathways.Finally,we discuss the possibility of using the microbiome as a biomarker to determine the stage and prognosis of COPD and the feasibility of developing a novel,safe,and effective therapeutic target.